INTRODUCTION — The term thoracic central venous obstruction (TCVO) encompasses a spectrum of disease affecting the veins in the chest that varies considerably in etiology, manifestations, implications, and approach to therapy. TCVO is a significant medical condition that can affect the ability to provide necessary care due to loss of venous access sites and can also impair upper extremity functioning and quality of life. Treatment of TCVO is tailored to address symptoms when they occur and the underlying venous and other anatomic abnormalities.
An overview of the etiologies, clinical presentations, and treatment of TCVO is reviewed. Specific etiologies are discussed in more detail separately.
●(See "Catheter-related upper extremity venous thrombosis in adults".)
●(See "Central vein obstruction associated with upper extremity hemodialysis access".)
●(See "Malignancy-related superior vena cava syndrome".)
●(See "Primary (spontaneous) upper extremity deep vein thrombosis".)
DEFINITIONS — Obstruction of venous flow can be described as central (nearer the heart) or peripheral (away from the heart). Central and peripheral venous obstruction can relate to the upper or lower extremity. Definitions surrounding iliocaval and/or lower extremity venous obstruction are reviewed separately. (See "Overview of iliocaval venous obstruction".)
Thoracic central venous obstruction — TCVO refers to obstruction of systemic (ie, central) veins located in the chest (ie, thoracic) cavity. As described below, this includes the subclavian veins, the thoracic segment of the internal jugular veins, brachiocephalic veins, the superior vena cava, and the suprahepatic portion of the inferior vena cava (figure 1). TCVO may be related to venous luminal narrowing that impedes blood flow (partially or completely) due to a variety of causes (eg, intimal hyperplasia, scarring, thrombus, external compression). Thrombosis of thoracic central veins (ie, thrombotic TCVO) is synonymous with deep vein thrombosis (DVT); moreover, thrombosis of the more peripheral upper extremity veins (eg, axillary, brachial) can also lead to TCVO.
Upper extremity venous obstruction — TCVO is distinguished from upper extremity venous obstruction, which refers to obstruction of the deep or superficial veins of the upper extremity. The deep veins of the upper extremity include the axillary veins, the single or paired brachial veins, and paired forearm veins (radial, ulnar, interosseous). The main superficial veins of the upper extremity include the cephalic (lateral), basilic (medial), cubital, and antecubital veins. Upper extremity venous obstruction may also be partial (ie, stenosis) or complete (ie, occlusion), but due to the smaller size of the involved veins and lower flow, stenosis of upper extremity veins often results in complete thrombosis.
The most common etiology for upper extremity venous obstruction is due to indwelling central venous catheters or from pacemaker wire leads. In addition, advanced axillary lymphadenopathy can compress the axillary vein and present as a thrombotic axillary venous outflow condition associated with inflammatory breast cancer [1]. (See "Catheter-related upper extremity venous thrombosis in adults".)
Deep vein thrombosis — Thrombosis of the thoracic central veins (ie, thrombotic TCVO) and/or deep veins of the upper extremity constitutes DVT. Thrombosis of the thoracic central veins is often contiguous with thrombosis of the deep vein of the upper extremity or may occur in addition to upper extremity deep venous thrombosis as part of a systemic response.
Thrombosis of the deep veins of the upper extremity constitutes upper extremity DVT. As in the lower extremity, primary upper extremity DVT is present when there is no discernable cause, and secondary upper extremity DVT is present when an inciting cause (eg, intravenous catheter) is present. Thrombosis of the deep veins of the upper extremity veins is often caused by indwelling central venous catheters and is reviewed separately. (See "Peripherally inserted central catheter (PICC)-related venous thrombosis in adults".)
CENTRAL VENOUS ANATOMY — Venous obstruction is defined as a luminal narrowing that impedes venous blood flow. A full understanding of the thoracic vascular anatomy and the anatomy of the thoracic outlet helps guide our understanding of the etiology and also highlights available options for treatment, which may include surgery.
The central venous system is divided into two components: the thoracic central venous system (TCVS) and the iliocaval (pelvic) central venous system. The components of the TCVS are reviewed. The iliocaval venous system is reviewed separately. (See "Overview of iliocaval venous obstruction", section on 'Iliocaval anatomy'.)
In addition to the central (ie, systemic) veins, other veins within the chest include the somatic veins (eg, azygos/hemiazygos), superficial veins, chest wall veins, or visceral veins (eg, pulmonary veins, coronary sinus). Somatic veins relate to the trunk or body wall and are also known as parietal veins. In general, these provide drainage of structures with voluntary innervation whereas the visceral veins generally provide drainage to structures with autonomic, involuntary innervation.
Thoracic central veins — A multidisciplinary committee has published reporting standards for central venous disease and presents what we feel should be adopted as a standard definition [2]. The TCVS consists of those veins located inferior to the thoracic outlet "superior thoracic aperture," central to the inner margin of first rib, and superior to the diaphragmatic hiatus (figure 1) [3]. The components of the system are as follows:
●Intrathoracic segments of internal jugular veins – The internal jugular (IJ) veins have a cervical and a central portion. The central portion begins at the superior margin of the first rib and passes through the thoracic outlet. It terminates posterior to the center of the sternal head of the clavicle by merging with the subclavian (SC) vein to form the brachiocephalic (BC) vein.
●Subclavian veins – The SC veins are the central continuation of the axillary veins, beginning just medial to the confluence of the cephalic arch and axillary vein (figure 2), where the SC vein crosses in a special groove over the superior surface of the first rib, merging with the central portion of the IJ veins to form the BC vein.
●Brachiocephalic veins – The BC veins originate at the confluence of the IJ and SC veins. The left BC vein meets the right BC vein to the right of the midline and posterior to the manubrium to form the superior vena cava (SVC).
●Superior vena cava – The SVC (figure 3) originates at the confluence of the right and left BC veins and extends to the right atrium, terminating posterior to the right atrial appendage at the superior cavoatrial junction. This is approximately 2.5 vertebral body units (one vertebral body with one adjacent intravertebral disc) inferior to the carina [4].
●Suprahepatic portion of the inferior vena cava – The suprahepatic inferior vena cava (IVC) originates at the inferior cavoatrial junction and extends to the level of the diaphragm.
Collateral venous circulation — Collateral venous flow refers to the condition in which alternative paths for blood flow emerge when the main venous pathways are obstructed.
When TCVO develops, drainage of venous blood will rely mainly on other veins including the azygos and hemiazygos veins; less commonly, venous return will depend on the superficial, paraspinal, epidural, and body wall veins. It is important to mention that the azygos vein ascends from the abdomen into the chest, turning anteriorly to drain directly into the posterior wall of the SVC, and it joins the SVC between the confluence of the BC veins superiorly and the right atrium (figure 3). Therefore, occlusion of SVC at that location is considered the most severe type of TCVO, as it hinders all possible collateral venous drainage when central veins are occluded and in that condition reverses flow in the azygos vein into the lower venous system and the IVC (image 1).
In addition, shoulder collaterals become (picture 1) very visible with advanced TCVO. It may involve the lateral thoracic vein, subscapular vein, suprascapular vein, and intercostal veins. In TCVO, shoulder collaterals can then bypass the blockage by direct drainage into the SC and axillary system or drain into the azygos system via the chest wall. It has been reported that the costoaxillary veins in advanced TCVO can connect the first to seventh intercostal veins to the lateral thoracic vein [5].
Uncommon collaterals include veins within the mediastinum and the pulmonary vasculature [6].
Thoracic outlet — The thoracic outlet is the space between the clavicle (collarbone), the first rib, and multiple muscles/ligaments.
As the subclavian-axillary vein crosses from the axilla to the chest, the venous structure passes through two important anatomic spaces, which can become narrowed, leading to venous compression [7].
●The interscalene triangle (figure 4) is the space between the first rib and scalene muscles (anterior and middle). Through this triangle, the SC artery and brachial plexus cross to the upper extremity.
●The costoclavicular space (figure 5) is a location where the subclavian-axillary venous segment is vulnerable to external compression at the junction of the first rib, clavicle, the subclavius muscle, and the costoclavicular ligament (Halsted ligament) [8]. This triangle is crucial in developing TCVO, and it may create the anatomic "nutcracker" effect of the first rib and clavicle [9]. In addition, hypertrophied subclavius muscle or costoclavicular ligament may introduce additional pressure to the tight space of the costoclavicular junction [10-12].
A significant number of thoracic central vein stenotic lesions occur at the junction of the first rib and the clavicle (ie, costoclavicular junction, thoracic outlet). It is felt that some, if not many, of these are related at least in part to external compression [13,14]. In one study, 48 cases were reviewed retrospectively, looking for extrinsic compression of the left BC vein [15]. The presence of collaterals was noted as well as the presence of any intrinsic stenosis of the left BC or SC veins. Some degree of extrinsic compression was observed in 21 patients (44 percent). Twelve (25 percent) had mild compression, six (13 percent) had moderate compression, and three (6 percent) had severe compression. Collateral veins were seen in 11 of 21. All three patients with severe extrinsic compression were symptomatic and were treated with stent placement.
An accessory muscular band that crosses the axilla may cause TCVO, and this unusual anatomic variant is referred to as Langer axillary arch, and in most cases dividing that aberrant muscular band is an essential element of treatment and is needed for full recovery [10]. Hypertrophy of the anterior scalene muscle (which lies behind the SC vein), the subclavius muscle underlying the clavicle, and the costoclavicular ligament may all further reduce the costoclavicular space in the anterior portion of the thoracic outlet and cause TCVO.
CLASSIFICATION — Based on clinical presentation, TCVO can be classified by the presence or absence of thrombus as either thrombotic or nonthrombotic, respectively. TCVO is also classified based on whether there is an inciting etiology (ie, secondary) or not (ie, primary).
●TCVO is commonly classified as thrombotic or nonthrombotic based on the presence or absence of thrombus, respectively, within the vein. A subset of patients have symptoms but no thrombosis, which is termed intermittent obstruction (ie, McCleery syndrome) [16,17]. (See 'Intermittent partial nonthrombotic obstruction' below.)
●TCVO can also be classified as primary or secondary depending upon whether there is an inciting etiology. Secondary obstruction of the thoracic central veins is more common compared with primary (direct) causes and is usually associated with indwelling catheters or wires that occupy a significant proportion of the cross-sectional diameter of the vessel. Primary TCVO is classified as traumatic (iatrogenic, gunshot, stab) or as effort thrombosis (also known as Paget-Schroetter syndrome). (See "Overview of blunt and penetrating thoracic vascular injury in adults" and "Primary (spontaneous) upper extremity deep vein thrombosis".)
●TCVO can be due to due to endoluminal pathology or external compression from adjacent structures or pathology. (See "Malignancy-related superior vena cava syndrome".)
●Obstruction may be partial (ie, stenotic lesion, nonocclusive thrombus) or complete (ie, occlusive lesion; chronic venous changes, occlusive thrombus) [2].
●TCVO can be classified anatomically based on the location of affected veins. Reporting standards published by a committee of the Society of Interventional Radiology present a comprehensive review of issues that should be determined in evaluating patients and for reporting data dealing with this condition (figure 6) [2]. An important aspect of this document is the establishment of an anatomic classification for TCVO reflecting increasingly severe degrees of involvement.
ETIOLOGIES
Intravascular device related — Intravascular devices placed into the thoracic central venous system are the most common cause of TCVO, primarily related to indwelling catheters positioned in or traversing through the subclavian (SC) vein [18-22]. Owing to the larger caliber of the catheter, TCVO is an ongoing clinical concern in patients dialyzed through an upper-extremity catheter in whom TCVO is reported to occur in up to 30 percent (image 2 and image 3) [23]. Wires for pacemakers and defibrillators may have similar effects on the central venous system [24]. (See "Central vein obstruction associated with upper extremity hemodialysis access".)
It is intuitive that indwelling catheter-induced trauma after insertion into the central venous system can damage venous endothelium to initiate a chain of local and systemic inflammatory responses, which can result in stenosis, scarring, and/or obstruction of the central venous system. In addition, the turbulence of flow from the catheter may add intimal hyperplasia, which could augment the degree of stenosis/occlusion of the central venous system [25,26].
Autopsy studies have demonstrated that intimal injury associated with focal endothelial denudation occurs acutely due to mechanical irritation from an indwelling foreign object [27]. In addition, the high-flow state induced by an indwelling catheter causes regions of increased turbulence that can also cause injury [28-30].
Chronic changes include focal attachments to the vein wall with thrombus, increased smooth muscle cells, vein wall thickening, and eventually collagen deposition. If a central venous catheter is observed with fluoroscopy, it can be seen to be in constant motion due to the movements of mediastinal structures created by the beating of the heart and the motions associated with respiration. Anatomic differences between right-sided and left-sided thoracic central veins and differing incidences of stenosis from side to side support the mechanical trauma theory [31-34].
Any intravenous catheter has the potential to cause venous thrombosis. These include tunneled and nontunneled central venous catheters, port devices, and peripherally inserted central catheters (PICCs) [35-38].
●Nontunneled catheters – The propensity for nontunneled catheters to cause TCVO, as well as the marked increase in the incidence of catheter-related infection, limits the duration of their use. In addition, some nontunneled catheters (eg, hemodialysis) are relatively stiff, resulting in increased mechanical trauma to the vein during insertion. (See "Overview of acute and emergency central venous access in adults".)
●Tunneled catheters – The frequency with which prior central catheter use caused TCVO in hemodialysis patients varies according to the vein used for catheter introduction, the type of catheter that is used, the duration of catheter use (ie, catheter contact time), and the number of catheters that have been placed. (See "Central vein obstruction associated with upper extremity hemodialysis access".)
●Peripherally inserted central catheters – The incidence of TCVO for PICCs is between 5 and 15 percent for hospitalized patients and 2 to 5 percent for ambulatory patients [39]. In a study in which venography was performed before and after insertion of PICCs in 150 patients, 7.5 percent of patients with previously normal central veins developed angiographic abnormalities after PICC placement (central venous stenosis in 4.8 percent, central venous occlusion in 2.7 percent) [40-45]. Of note, many of these thrombotic events may be clinically asymptomatic. (See "Peripherally inserted central catheter (PICC)-related venous thrombosis in adults".)
●Cardiac implantable electronic devices (CIEDs) have also been associated with TCVO. The pathogenesis for the development of stenosis in association with the transvenous leads of a CIED is thought to be mechanical irritation. These leads are generally introduced through the SC vein, which is the most frequently involved vessel. However, the brachiocephalic (BC) vein and superior vena cava (SVC) can also be involved. In some patients, SVC syndrome has developed in association with both a catheter and transvenous CIED leads passing through the SVC. (See "Clinical features, diagnosis, and classification of thoracic central venous obstruction", section on 'Edema and pain'.)
A variety of catheter-related factors influence the incidence and severity of TCVO. These are reviewed briefly and discussed in more detail separately. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Catheter-related factors'.)
●Catheter diameter – The diameter of the catheter relative to the size of the vein (so-called "catheter-to-vein ratio") determines whether blood flows freely around the catheter or stagnates [46-48]. For a vein of similar size, thrombosis is more likely with a larger diameter catheter (eg, plasmapheresis, hemodialysis, multilumen catheters) compared with a smaller catheter (eg, single lumen or smaller gauge).
●Insertion site and lesion location – Although SC and internal jugular (IJ) cannulation sites are more commonly blamed for TCVO, peripheral insertion sites for central venous catheters are also associated with an increased incidence of venous stenosis [40,49-51].
•For IJ catheters, a left-sided catheter may be more commonly involved [31-34]. A left-sided catheter must be longer due to the greater distance required to traverse the chest, and the catheter must traverse several anatomic angulations [52]. These are located between the left IJ and left BC vein, an angle created as the BC vein crosses over the BC artery and aorta where the vein is subjected to pulsations and potentially extrinsic compression [15], and lastly between the left BC vein and SVC [53]. The left IJ vein also has a smaller cross-sectional area compared with the right IJ vein [54].
•For SC catheters, the sharp curve at the junction of the SC and BC veins along with the movement of these structures with the beating of the heart and respiratory movement is thought to result in endothelial injury both during insertion and the life of the catheter, possibly leading to neointimal hyperplasia.
●Catheter malposition – Malposition of the tip of a central catheter may be associated with an increased risk of TCVO. (See "Malfunction of chronic hemodialysis catheters" and "Peripherally inserted central catheter (PICC)-related venous thrombosis in adults", section on 'Device factors'.)
●Catheter-related infection – A relationship between TCVO and catheter-related infection has also been reported. However, it should be noted that accurate evaluation of the relationship between catheter-associated infection and TCVO is difficult because of multiple confounding variables [55-57]. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Epidemiology, pathogenesis, clinical manifestations, and diagnosis" and "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention".)
●Irritant or vesicant phlebitis – Thrombosis can occur as a reaction to the catheter material or to the infused drugs contacting the venous intima. Common culprits include potassium chloride, diazepam, certain antibiotics (eg, vancomycin and oxacillin), chemotherapy agents, and hypotonic (<250 mOsm/kg) or hypertonic (>350 mOsm/kg) electrolyte solutions [58]. Some such agents also have irritant or vesicant properties and can cause necrosis of the subcutaneous tissues if leakage outside the vein occurs (table 1 and table 2). It is important to note that not all vesicant agents cause venous irritation during the injection. For this reason, verification of the central location (ie, cavoatrial junction) of the catheter tip is essential when infusing these agents. (See "Central venous access: Device and site selection in adults", section on 'Nature of infusate' and "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".)
●Hormonal factors – An association between hormonal influences and primary (ie, non-catheter-related) TCVO has been established. Observational studies suggest that patients who receive PICCs during pregnancy for a variety of indications experience a high rate of thrombosis [59,60]. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis".)
Oral contraceptives may increase the risk for catheter-related TCVO when used in a patient with prothrombotic mutations, such as prothrombin 20210 or factor V Leiden [61,62]. Case reports of catheter-related TCVO (with or without coagulation abnormalities) are also reported to occur with ovulation induction and in vitro fertilization [63-65]. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Venous thromboembolism'.)
Postthrombotic syndrome — Prior deep vein thrombosis (DVT) also increases the risk for subsequent venous thrombosis, particularly in the setting of central venous catheter placement [46,66]. (See "Post-thrombotic (postphlebitic) syndrome".)
Malignant obstruction — Malignancies that more typically lead to right-sided thoracic venous obstruction and SVC syndrome include lung cancer and non-Hodgkin lymphoma, which are responsible for approximately 95 percent of the cases of malignancy-related SVC syndrome. (See "Malignancy-related superior vena cava syndrome", section on 'Typical malignancies'.)
Advanced axillary lymphadenopathy and compression on axillary vein can also obstruct axillary venous outflow (eg, inflammatory breast cancer).
Aneurysmal disease or aortic ectasia — One of the more frequent causes of external venous compression occurs when there is ectasia of the aortic arch or its branches [67]. When this occurs, a deformity of the left BC vein may be seen on imaging. Support suggesting that this deformity is causing a true obstruction can be confirmed by the presence of collateral veins peripheral to the deformity. It is important that this situation is recognized for what it is; attempts to dilate the vein with an angioplasty balloon will have no effect. Some have suggested stenting in cases with significant symptoms; however, placement may be difficult owing to the large size of the vein [15]. (See "Overview of aneurysmal disease of the aortic arch branches or upper extremity arteries in adults".)
Iatrogenic or traumatic vessel injury — Thoracic venous injuries are predominantly due to traumatic and iatrogenic causes [68]. The narrow space of the costoclavicular region in combination with repeated trauma can lead to intrinsic damage to the tunica intima, flow turbulence, and intimal hyperplasia, which in turn could result in the activation of the coagulation cascade and initiate the thrombus formation. Long-standing external trauma to the subclavian/axillary vein will also result in scarring and fibrosis of the vein (image 4). Clavicular fracture has also been reported as a cause of subclavian-axillary venous thrombosis [68,69]. (See "Overview of blunt and penetrating thoracic vascular injury in adults".)
Venous thoracic outlet syndrome — Thoracic outlet syndrome (TOS) is an anatomic disorder first described in 1956 as bony (image 5 and figure 7), muscular, or ligamentous compression of the brachial plexus, arteries, and veins as they cross through the thoracic outlet space (image 6) between the clavicle and upper ribs [70]. Compression by subclavius and anterior scalene muscles has also been reported (ie, McCleery syndrome) [71].
The manifestations of TOS is usually related to compression of any of these three structures (figure 5); however, a combination of structures and symptoms may also occur (figure 5) [19,72,73]. Among the three main types of TOS (neurogenic, arterial, venous [vTOS]), vTOS comprises 5 percent of cases (image 7) [74]. (See "Overview of thoracic outlet syndromes" and "Primary (spontaneous) upper extremity deep vein thrombosis".)
The presentation of vTOS can be thrombotic (more common) or nonthrombotic. The most common clinical presentation of thrombotic vTOS is acute thrombosis of subclavian-axillary vein segment (ie, Paget-Schroetter syndrome), which typically affects young, high-performance, athletic individuals, or people who elevate their arms above the head for extended periods of time [75-77]. Acute thrombotic events are usually associated with arm swelling, bluish discoloration, numbness, and pain. In cases of advanced chronic occlusion, they are usually associated with extensive collateral pathways over neck, chest wall, and arms. Venous TOS is more common on the right, which in most cases reflects the dominant extremity [78,79]. (See "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Epidemiology and risk factors' and "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Clinical presentations'.)
Hypercoagulability — Congenital or acquired systemic prothrombotic conditions may increase the risk of TCVO [80-87]. Studies have also assessed the interaction between an underlying hypercoagulable state and the local injury caused by the indwelling central venous catheters [61,88].
A higher incidence (up to 32 percent) of symptomatic catheter-related upper extremity DVT is found in patients with underlying malignancies [89-91]. Patients with malignancy involving the right lung, lymph nodes, or other mediastinal structures can present with thrombosis due to central vein compression. (See "Risk and prevention of venous thromboembolism in adults with cancer" and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)" and "Malignancy-related superior vena cava syndrome".)
CLINICAL PRESENTATIONS — The clinical presentation of TCVO depends upon the acuity (acute, chronic), severity of obstruction (partial, complete), the location of the obstruction, and the extent of any venous compensation (ie, collateral flow).
Acute thrombosis — Acute thrombotic obstruction of the central veins can occur in the setting of a previously widely patent vessel (eg, previous history of venous thoracic outlet syndrome) or in a vein with a preexisting stenosis (stenotic veins from previous instrumentation or continuous chronic friction at the thoracic outlet). The patient is often aware when symptoms started and can generally relate their occurrence to any antecedent events.
Acute symptoms and signs of TCVO can include pain, swelling (upper extremity, neck, face), chest pain, respiratory symptoms (ie, related to pulmonary embolism), or neurologic manifestations (ie, related to paradoxical embolism, cerebral edema). (See "Clinical features, diagnosis, and classification of thoracic central venous obstruction".)
Intermittent partial nonthrombotic obstruction — The majority of cases of partial nonthrombotic obstruction present with intermittent symptoms (also called McCleery syndrome [17]).
Intermittent, nonthrombotic obstruction is associated with dull aching pain, engorged upper extremity superficial veins, and dependent swelling. In addition, most of these patients developed significant venous collaterals that help with the drainage of the arm (picture 2). Besides the swelling, hand cyanosis and pain (venous claudication) and paresthesias may be present as well [92].
One study highlighted the occurrence of intermittent ipsilateral arm swelling as an integral diagnostic component for those who presented with nonthrombotic TCVO [92]. Symptoms of intermittent obstruction mandate a targeted workup to rule out TCVO [93]. Subclavian-axillary vein compression can be provoked by upper arm abduction and demonstrated on venography (image 6) [94]. However, the Adson test (rotating head toward the ipsilateral extremity and feeling for loss of radial pulse during arm abduction) is not reliable, as it can be positive in up to 50 percent of the general population [95].
Chronic progressive occlusion — With complete venous occlusion, there is a triad of pain, cyanosis, and swelling [96,97]. Hand paresthesias associated with the swelling has been also reported secondary to anoxic nerve injury or from nerve compression from surrounding soft tissue edema [98]. Upper extremity swelling worsens with exercise or arm dependency [97]. The sequela normally starts with repetitive trauma to the subclavian vein and continues with compression at the costoclavicular region. In turn, this leads to the development of a sclerosed vein with damaged tunica intima along with intraluminal sclerotic web, which usually leads to venous outflow obstruction with subsequent propagation of a blood clot to the axillary vein. Significant superficial collateral venous engorgement is usually seen (image 8) [99].
DIAGNOSIS — A diagnosis of TCVO may be suspected based upon history and physical exam but requires demonstration of venous stenosis or obstruction affecting the thoracic central veins on venous imaging studies (algorithm 1). Duplex ultrasound is often the initial imaging modality for most patients with suspected TCVO to identify obstruction (image 9) and to evaluate for venous hypertension. Doppler ultrasound examination is also the standard tool used to evaluate any affected superficial veins and confirm upper extremity phlebitis. (See "Clinical features, diagnosis, and classification of thoracic central venous obstruction", section on 'Vascular imaging'.)
Additional studies may include computed tomographic (CT) or magnetic resonance venography (image 10 and image 11), or digital subtraction venography depending on the suspected etiology.
●(See "Catheter-related upper extremity venous thrombosis in adults", section on 'Vascular imaging'.)
●(See "Malignancy-related superior vena cava syndrome", section on 'Approach to imaging'.)
●(See "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Imaging'.)
CT pulmonary angiography is warranted in those with chest pain or dyspnea and to rule out pulmonary embolism.
MANAGEMENT
Asymptomatic — Asymptomatic nonthrombotic TCVO does not require specific treatment except in situations where improvement of venous outflow is necessary for a hemodialysis arteriovenous access candidate. Patients with central venous access devices who have a venous stenosis without thrombus but are otherwise asymptomatic can be observed.
Whether patients with asymptomatic nonthrombotic TCVO (ie, thoracic/upper extremity deep vein thrombosis [DVT]) should be treated is more controversial and less well defined than treatment of symptomatic thrombosis. While asymptomatic thrombosis in the lower extremity is well recognized as a source of embolization, the rate of this or other complications with asymptomatic thoracic central vein thrombosis is not known [100]. Consequently, the risk/benefit analysis of any potential treatment cannot be determined. However, there is no theoretical reason to believe that the risk of embolization is any different compared with symptomatic thoracic central vein thrombi, unless chronic in nature. In addition, asymptomatic upper extremity DVT can cause permanent obstruction in the subclavian vein and may result in loss of central venous access on the affected side. As an example of this last point, one series noted that 14 percent of patients undergoing a second or third catheter placement failed the procedure because of obstruction. Therefore, barring any contraindications, anticoagulation should be administered in accordance with the recommendations below. (See 'Anticoagulation' below.)
Symptomatic — Initial treatment of symptomatic TCVO is aimed at relieving symptoms, which includes reducing pain from associated superficial vein thrombosis and phlebitis, controlling limb edema, minimizing the risk for embolization by providing systemic anticoagulation for those with thrombotic obstruction (ie, upper extremity DVT), and providing for continued intravenous access, if it is needed. However, while anticoagulation reduces propagation of thrombus, it does little to resolve acute clot. Depending on the duration and severity of symptoms, subsequent treatment is tailored to address underlying venous and other anatomic abnormalities through venous intervention or surgery. (See 'Anticoagulation' below and 'Endovenous intervention' below and 'Etiology-specific considerations' below.)
Thoracic/upper extremity DVT secondary to intravenous catheters is generally managed more conservatively compared with primary, spontaneous upper extremity TCVO. The more aggressive approach used with spontaneous thrombosis is due to a higher incidence of postphlebitic sequelae. In a systematic review, the incidence of postthrombotic syndrome (PTS) ranged from 7 to 46 percent following upper extremity DVT in adults [101]. Residual thrombosis and axillosubclavian vein thrombosis were associated with PTS, but catheter-associated upper extremity DVT was associated with reduced risk. (See "Primary (spontaneous) upper extremity deep vein thrombosis".)
Superficial vein thrombosis and phlebitis may accompany thrombotic TCVO and may be more commonly associated with catheter-related TCVO, particularly the use of peripherally inserted central venous catheters (PICCs). Phlebitis and PICC-related thrombosis may occur in up to 28 percent of patients [89,102]. There are limited data to guide management of upper extremity superficial vein thrombosis and phlebitis and much of the care is extrapolated from studies of the lower extremity, including limb elevation, nonsteroidal anti-inflammatory agents, compression therapy. The role of anticoagulation in the management of upper extremity superficial vein thrombosis and phlebitis not associated with DVT (ie, TCVO) is reviewed elsewhere. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Superficial vein thrombosis and phlebitis'.)
Thrombotic TCVO — Despite a lack of direct evidence proving safety and efficacy of anticoagulation for thoracic/upper extremity DVT, anticoagulation for three months with adjunctive venous intervention in selected patients remains the cornerstone of therapy with a goal of relieving acute symptoms and preventing embolization (algorithm 1) [103-106].
Anticoagulation — For patients with thrombotic TCVO (ie, thoracic/upper extremity DVT), we recommend anticoagulation as described for iliocaval/lower extremity DVT, provided there are no contraindications. This recommendation is consistent with guidelines from the American College of Chest Physicians and other international guidelines [105,107-109]. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Patients at low risk of bleeding'.)
Pulmonary embolism is overall less common for patients with thrombosis involving the thoracic central veins/upper extremity veins, compared with lower extremity DVT [110,111]. Nevertheless, venous thromboembolism is still a serious problem. Thus, therapy for TCVO/upper extremity DVT is directed toward preventing this complication. Anticoagulation is generally effective for preventing pulmonary embolism in patients with lower extremity DVT. By inference, anticoagulation should also be effective for preventing embolization from thrombosed thoracic/upper extremity veins, although treatment failures occur at both locations [112]. However, no treatment scheme has been rigorously evaluated for its efficacy in preventing embolization from upper extremity sources. As a result, recommendations for the treatment of thoracic/upper extremity DVT are based largely upon indirect evidence from the experience with DVT of the lower extremities. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)".)
The author's practice is to offer full anticoagulation therapy for three months, if not contraindicated, for patients who present acutely (<14 days) or subacutely (ie, between 14 days and three months) from the onset of symptoms, but no anticoagulation for those who present chronically (ie, after three months). Chronic fibrotic obstruction of subclavian/axillary veins is associated with a delayed presentation. Patients with chronic symptoms related to TCVO are less likely to benefit from anticoagulation, and even after successful endovenous or surgical intervention, these patients have poorer outcomes [113].
The type and intensity of anticoagulation is like recommendations to prevent embolization of thrombi from the deep veins of the lower extremities. We suggest initial therapy with parenteral anticoagulants (low-molecular-weight heparin [LMWH], fondaparinux, unfractionated heparin) followed by LMWH or a vitamin K antagonist (eg, warfarin). Sufficient data are lacking to recommend the use of a direct oral anticoagulant (DOAC) for the management of the acute phase of thoracic/upper extremity DVT. However, observational and small controlled studies examining the utility of DOACs in upper extremity thrombosis are emerging [114,115]. Therapeutic options for DVT are discussed in detail elsewhere. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)".)
The optimal strategy for patients who have contraindications to systemic anticoagulation is unknown. Venous intervention may be performed but must be considered on a case-by-case basis. The use of superior vena cava (SVC) filters remains one of the most controversial issues among clinicians and there are no randomized studies to support routine use. Their use should be limited to those with contraindications to anticoagulation and documented pulmonary embolism. Because of the lower risk of clinically significant pulmonary embolism in upper extremity DVT, potential benefit must outweigh the significant risks of SVC filter placement, including filter embolization or filter thrombosis. In one review, 3 percent had major filter-related complications [116]. These included SVC perforation in 6, cardiac tamponade in 4, aortic perforation in 2, SVC thrombosis in 2, and pneumothorax in 1.
Endovenous intervention — Endovenous intervention has revolutionized the ability to address and treat TCVO. Endovenous intervention may help reduce the long-term sequelae of the thrombotic event (ie, postthrombotic syndrome). For those with severe manifestations of TCVO, such as SVC syndrome or phlegmasia cerulea dolens, endovenous intervention can be life- or limb-saving. Appropriate expertise and institutional resources must be available to provide this intervention. If such resources are not available, patients with severe symptoms should be considered for transfer, and for others, anticoagulation with interval follow-up vascular imaging is a reasonable alternative. (See "Endovenous intervention for thoracic central venous obstruction".)
The goals of endovenous intervention in those with acute thrombotic (<14 days) TCVO is to decrease the volume of thrombus using catheter-directed thrombolysis (CDT), if not contraindicated (table 3), and then to evaluate for any underlying intrinsic venous stenosis and, if present, perform angioplasty with or without stenting of the diseased vein segment depending on the likely etiology. However, for those with TCVO due to venous thoracic outlet syndrome (vTOS), venous stenting should be avoided prior to thoracic outlet decompression. Moreover, most patients with catheter-related thoracic/upper extremity DVT do not need catheter-directed thrombolytic therapy, although some authors have advocated its use. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Treatment'.)
Early diagnosis is critical, and in the author's opinion, it is acceptable to perform CDT up to 14 days from the onset of symptoms. The effectiveness of endovenous intervention has been well reported. Many experts have shown a recanalization rate up to 80 percent with early CDT (≤14 days) [117,118]. On the other hand, patency rate drops significantly to 29 percent after two weeks [119].
Because thrombolytic therapy aims to minimize long-term symptoms, the impact on the patient's quality of life should first be determined. Catheter-directed thrombolytic therapy may be reasonable for individuals with significant symptoms in the acute stages of thrombosis (symptoms less than 14 days) who have met all of the following criteria (see "Endovenous intervention for thoracic central venous obstruction"):
●Have not adequately responded to systematic anticoagulation
●Have a low risk for bleeding
●Have a good long-term prognosis relative to their underlying disease
●Have a lifestyle that requires vigorous use of the affected arm
Patients who do not meet these criteria (eg, a patient with limited life expectancy from their coexistent medical problems who does not require extensive use of their arm) are likely to do just as well with conservative therapy, consisting of symptomatic care and anticoagulation.
Nonthrombotic TCVO — For patients with nonthrombotic obstruction and moderate-to-severe symptoms such as swelling and pain, treatment is targeted toward reducing the severity of the stenotic venous lesion using angioplasty with or without stenting (image 12 and image 13) depending on the likely etiology. (See "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Thrombolytic therapy'.)
For those with chronic onset TCVO, or those with incidental thrombus, the treatment approach is according to the presenting symptoms. As examples:
●No specific treatment is recommended for patients without symptoms, even if thrombus is found incidentally.
●A young, healthy patient with significant symptoms may benefit from an aggressive approach (ie, thoracic outlet decompression and venous reconstruction) whereas a frail, older adult will not fit for such approach.
It is important to recognize external compression; attempts to dilate the vein with an angioplasty balloon will have no effect. Some have suggested stenting in cases with significant symptoms; however, placement of a stent may be difficult owing to the large size of the vein, and in those with costoclavicular compression, stenting is ill advised, as it is ineffective, may result in stent fracture, and complicates subsequent surgical management [15].
Etiology-specific considerations
●Catheter-related – Indwelling catheters or wires contribute to most cases of TCVO. Anticoagulation and angioplasty with or without stenting are the main components of the therapy. Whether to remove an indwelling device depends upon the ongoing need for the device, and whether it is functioning or occluded. (See "Catheter-related upper extremity venous thrombosis in adults", section on 'Catheter management' and "Malfunction of chronic hemodialysis catheters", section on 'Catheter-related central venous thrombosis'.)
●Managing hemodialysis arteriovenous access – Patients on hemodialysis with hemodynamically and clinically significant central venous stenosis benefit from venous intervention to restore central venous patency. (See "Central vein obstruction associated with upper extremity hemodialysis access".)
These patients should also be carefully evaluated for possible vTOS. Affected patients may benefit from periclavicular first rib resection, scalenectomy, and venolysis [120]. Interestingly, patients with chronic vTOS benefit as much from decompression as those with acute vTOS [121].
●Thoracic outlet decompression – Thrombotic vTOS is often managed with systemic anticoagulation followed by CDT, if not contraindicated. First rib resection may be appropriate in selected patients, taking into consideration the severity of symptoms, adequacy of collateral circulation, and intended activity level. Many respected authorities have recommended infraclavicular first rib resection followed by concomitant postoperative venous balloon angioplasty in same admission with excellent midterm outcomes [122,123]. Anticoagulation alone is not recommended secondary to poor outcomes, and thoracic outlet decompression surgery should follow within the same admission or within six to eight weeks [117]. (See "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Thoracic outlet decompression'.)
●Treatment of malignancy – Treatment of TCVO will depend on the clinical presentation and the severity of TCVO in addition to timing of other oncological treatment as radiation of chemotherapy. Even with thrombotic TCVO secondary to indwelling catheter, we prefer to start full anticoagulation and to leave catheters in place until completion of therapy, and then it might be removed. (See "Malignancy-related superior vena cava syndrome".)
●Traumatic injury – For patients who present with acute venous obstruction related to iatrogenic or traumatic injury, venous repair may be warranted. (See "Overview of blunt and penetrating thoracic vascular injury in adults", section on 'Great vessel injury'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism" and "Society guideline links: Venous access" and "Society guideline links: Chronic venous disorders".)
SUMMARY AND RECOMMENDATIONS
●Thoracic central venous obstruction – Thoracic central venous obstruction (TCVO) encompasses a spectrum of conditions affecting the veins in the chest. The most common cause of TCVO is vein injury related to placement of intravascular devices into the thoracic central venous system (TCVS), primarily indwelling central venous catheters and pacemaker leads. Other etiologies include conditions that injure or compress the vein (eg, thoracic outlet syndromes, malignant obstruction, aneurysmal disease) and conditions that increase the risk for venous thrombosis. (See 'Introduction' above and 'Etiologies' above.)
●Anatomy and collateral venous flow – The TCVS includes the intrathoracic portion of the internal jugular veins, the subclavian veins (figure 8), and the brachiocephalic veins bilaterally, which join to form the superior vena cava (SVC). When TCVO develops, drainage of venous blood relies mainly on the azygos and hemiazygos veins to return blood to the heart (figure 3). Occlusion of SVC impairs azygous flow and leads to the most severe type of TCVO. (See 'Central venous anatomy' above and 'Collateral venous circulation' above.)
●Classification – TCVO is classified based on the presence of an inciting etiology (ie, secondary) or not (ie, primary). TCVO can be also classified anatomically based on the location of affected veins (figure 6). TCVO is either thrombotic or nonthrombotic based upon the presence or absence of thrombus, respectively. (See 'Classification' above.)
●Clinical presentations – The clinical presentation of TCVO varies depending on the time course of symptoms (acute, intermittent, chronic), severity of obstruction (partial, complete), location of obstruction, and the extent of any venous compensation (ie, collateral flow). Symptoms range from mild to severe and include predominantly pain and edema (extremity, facial), but other symptoms can occur. (See 'Clinical presentations' above.)
●Diagnosis – A diagnosis of TCVO may be suspected based upon history and physical exam but requires demonstration of the stenotic lesion or thrombus affecting the thoracic central veins on venous imaging studies. (See 'Diagnosis' above.)
●Treatment – Treatment of symptomatic TCVO is aimed at relieving symptoms, which includes reducing pain from phlebitis and preventing pulmonary embolism for those with thrombotic obstruction. Subsequent treatment of symptomatic TCVO is tailored to address underlying venous and other anatomic abnormalities using a variety of endovascular and surgical options. Asymptomatic TCVO does not require specific treatment except when needed to improve venous outflow for hemodialysis arteriovenous access. (See 'Management' above.)
●Anticoagulation – For patients with thrombotic TCVO (ie, thoracic/upper extremity deep vein thrombosis), we suggest anticoagulation (Grade 2B). For uncomplicated cases, three months of anticoagulation therapy should be sufficient. A longer duration of anticoagulation may be warranted when a central venous catheter is left in place, particularly for patients with malignancy. (See 'Anticoagulation' above and "Catheter-related upper extremity venous thrombosis in adults", section on 'Treatment'.)
●Catheter-directed thrombolytic therapy – For patients with thrombotic TCVO with severe symptoms of duration <14 days, we suggest catheter-directed thrombolytic therapy for patients who meet the following criteria (Grade 2C) (see 'Endovenous intervention' above):
•Does not have catheter-related venous thrombosis
•Has not adequately responded to systematic anticoagulation
•Has a low risk for bleeding
•Has a good long-term prognosis relative to their underlying disease
•Has a lifestyle that requires vigorous use of the affected arm
