Venous thoracic outlet syndrome (TOS) is uncommon but occurs in young, healthy patients, typically presenting as subclavian vein (SCV) effort thrombosis. Venous TOS arises through chronic repetitive compression injury of the SCV in the costoclavicular space with progressive venous scarring, focal stenosis, and eventual thrombosis. Diagnosis is evident on clinical presentation with sudden spontaneous upper extremity swelling and cyanotic discoloration. Initial treatment includes anticoagulation, venography, and pharmacomechanical thrombolysis. Surgical management using paraclavicular decompression can result in relief from arm swelling, freedom from long-term anticoagulation, and a return to unrestricted upper extremity activity in more than 90% of patients.
Key points
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The diagnosis of venous thoracic outlet syndrome (TOS) should be suspected in any young healthy individual presenting with spontaneous upper extremity swelling and cyanotic discoloration.
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Duplex ultrasound can detect axillary-SCV thrombosis but a negative study cannot exclude the diagnosis of venous TOS, so additional imaging is often needed.
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Therapeutic anticoagulation and prompt contrast venography are recommended, with catheter-directed thrombolysis and possible balloon angioplasty, as a bridge toward surgical treatment.
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Definitive surgical treatment of venous TOS can be performed by protocols involving either transaxillary, infraclavicular, or paraclavicular approaches to thoracic outlet decompression.
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The more complete paraclavicular approach for venous TOS, coupled with possible SCV reconstruction when necessary, has overall outcomes that exceed those attained with other approaches.
Introduction
Venous thoracic outlet syndrome (TOS) is distinguished from other types of TOS with regard to pathophysiology, clinical presentation, and functional consequences for the patient, and its management therefore requires different considerations and approaches from either neurogenic TOS or arterial TOS. Patients with venous TOS typically present with the axillary–subclavian vein (SCV) effort thrombosis (Paget-Schroetter) syndrome, characterized by sudden, spontaneous, upper extremity swelling and cyanotic discoloration, often accompanied by heaviness, easy fatigue, and pain ( Fig. 1 ).
The anatomy of venous TOS involves the path of the axillary vein to become the SCV as it continues centrally underneath the clavicle, through the costoclavicular space, and then joins with the internal jugular vein to form the innominate vein behind the sternoclavicular joint ( Fig. 2 ). , Even with the arm at rest, the space through which the SCV passes is relatively narrow, and it is narrowed further during arm elevation. In a patient who may be prone to develop venous TOS, the SCV is subject to repetitive compression between the clavicle, first rib, anterior scalene muscle, subclavius muscle, and the costoclavicular ligament. This can lead to gradual, progressive, focal venous stenosis at the level of the first rib, involving scar tissue formation, and contraction around the outside of the vein as well as fibrosis and thickening within the vein wall itself. The patient with venous TOS is initially unaware of this repetitive injury, in large part due to the simultaneous expansion of collateral veins that can effectively prevent upper extremity venous congestion. High-grade central venous stenosis ultimately causes stagnant and turbulent blood flow, however, with subsequent development of acute SCV thrombosis superimposed on the chronic stenosis. The peripheral growth of thrombus extending from the subclavian into the axillary vein results in further obstruction of critical collaterals, resulting in acutely impaired venous return and the clinical presentation of a swollen, cyanotic arm. Rarely, there are individuals with minimal collateral vein expansion during the early development of SCV stenosis, such that positional axillary-SCV compression can lead to significant venous congestion symptoms even in the absence of actual thrombosis (McCleery syndrome).
Patient evaluation overview
Clinical Presentation
Patients presenting with venous TOS are typically between 14 years and 45 years of age and otherwise healthy and physically active, and many present with a history of frequent repetitive overhead motion activity or heavy lifting with the affected extremity. Although venous TOS often occurs in competitive athletes, performance musicians, and manual laborers, this condition can arise even in sedentary individuals, and there is no clear gender predilection. The usual clinical presentation of patients with venous TOS is SCV effort thrombosis presenting with sudden swelling of the affected upper extremity and accompanying discomfort, heaviness, and cyanosis. This is evident on physical examination, with the affected extremity being markedly swollen and discolored from the shoulder to the hand. Multiple distended subcutaneous collateral veins may be visible in the arm and shoulder and on the anterior chest. Approximately 10% to 20% of patients with SCV thrombosis have non–life-threatening pulmonary embolism detectable by imaging studies, and in some patients the initial clinical presentation of venous TOS may be pulmonary embolism of obscure origin, with a negative evaluation for a source of deep vein thrombosis in the pelvis or leg. Because the majority of clot in venous TOS develops in the distal SCV past the site of focal stenosis in the costoclavicular space, the stenosis prevents central embolization of a significant amount of thrombus, making pulmonary embolism in this condition less threatening than that occurring with venous thrombosis in the pelvis or lower extremity.
Diagnostic Evaluation
SCV thrombosis due to venous TOS should be strongly suspected in any young, active, otherwise healthy person presenting with sudden, spontaneous whole-arm swelling, particularly in the absence of a significant medical history or previous placement of an SCV catheter. Upper extremity venous duplex ultrasound testing is often used to help establish the diagnosis and can be useful when the study is positive for axillary-SCV thrombosis. It must be recognized, however, that there are inherent technical limitations to duplex imaging of the central SCV due to acoustic interference by the clavicle, such that clot present only above the clavicle or a high-grade stenosis of the central SCV may be easily overlooked. Altered venous hemodynamics after SCV thrombosis may also be obscured if there is rapid flow through abundant venous collaterals. In a recent study from the authors’ medical center of 214 patients with surgically proved venous TOS, a false-negative rate of 21% was found for initial duplex ultrasound studies, and this was associated with a delay in more definitive diagnostic imaging, subsequent clot propagation, and a more frequent need for SCV bypass at the time of surgical treatment than in those with a positive initial duplex study ( Fig. 3 ). This has reinforced the authors’ recommendation that once a diagnosis of SCV effort thrombosis is considered based on clinical presentation, patients should be presumed to have SCV effort thrombosis due to venous TOS until proved otherwise and started on presumptive anticoagulation to limit clot progression, and definitive imaging should be obtained as early in the evaluation as feasible ( Fig. 4 ).
Definitive Diagnostic Imaging
Contrast-enhanced upper extremity computed tomography or magnetic resonance venography each can provide excellent imaging of the SCV, easily demonstrating SCV thrombosis; in addition, the absence of SCV obstruction can be visualized with sufficient accuracy to exclude a diagnosis of venous TOS when negative, particularly if the study is performed with the arms at the side and in overhead elevation. , These studies are ideally suited for patients who present at long intervals after the onset of symptoms (more than 6 weeks). In most cases of high clinical suspicion of venous TOS within 6 weeks of the onset of symptoms, however, it is recommended that direct catheter-based upper extremity venography be performed as soon as feasible, because this provides the most practical, efficient, and cost-effective approach to evaluating the patient with suspected SCV effort thrombosis.
Laboratory Studies
Hematological testing does not play a significant role is evaluation of patients with primary SCV thrombosis, because the pathogenesis of venous TOS is that of a localized mechanical disorder based on repetitive vein compression and its sequelae, rather than an increased systemic tendency toward thrombosis. , Although some studies have shown an incidence of abnormal thrombophilia testing similar to that found in the general population, others have suggested that there is an increased incidence of hypercoagulability in at least some patients with venous TOS. The authors currently do not recommend extensive hematological testing in patients with a sound clinical diagnosis of SCV thrombosis and venous TOS, in the absence of other vascular thromboembolic disease or recurrent SCV thrombosis.
Pharmacologic or medical treatment options
Based on the clinical suspicion of SCV thrombosis and venous TOS, it is recommended that therapeutic anticoagulation be started as soon as feasible to diminish clot propagation, even as addition testing is undertaken. The choices for initial anticoagulation include intravenous or subcutaneous forms of heparin, with conversion to one of several oral anticoagulants or subcutaneous heparin, as summarized in Table 1 , prior to discharge. There is no known role for antiplatelet therapy in this condition, either as an adjunct or substitute for anticoagulation.
| Drug Name | Dose | Mechanism of Action |
|---|---|---|
| Unfractionated heparin | IV titrated to PTT a | Binds enzyme antithrombin III inhibitor |
| Advantages | Easy to titrate and reverse | |
| Disadvantages | Requires hospital admission for IV access | |
| Half-life and reversal | 0.5–2 h | Protamine |
| Low-molecular-weight heparin (Lovenox) | 1 mg/kg BID | Binds enzyme antithrombin III inhibitor |
| Advantages | Weight-based dosing, can monitor anti–factor Xa activity | |
| Disadvantages | Requires twice-daily subcutaneous injections | |
| Half-life and reversal | 4.5–7 h | Protamine |
| Warfarin (Coumadin) | PO adjusted to INR b | Inhibits vitamin K–dependent factors c |
| Advantages | Very inexpensive, large historical experience | |
| Disadvantages | Blood draws, poor compliance, frequent dose changes, dietary limits | |
| Half-life and reversal | 36–40 h | Fresh frozen plasma |
| Dabigatran (Pradaxa) | 75–150 mg BID | Direct thrombin inhibitor |
| Advantages | No monitoring or dietary limitations needed | |
| Disadvantages | Expensive, contraindicated in renal failure, some hospitals may not have rapid access to reversal | |
| Half-life and reversal | 12–17 h | PCC, monoclonal antibody (Praxbind) |
| Rivaroxaban (Xarelto) | 10 mg, 15 mg, or 20 mg QD | Factor Xa inhibitor |
| Advantages | No monitoring needed, daily dosing | |
| Disadvantages | Expensive, some hospitals may not have rapid access to reversal | |
| Half-life and reversal | 5–9 h | PCC, recombinant Xa (Andexxa) |
| Apixaban (Eliquis) | 2.5 mg or 5 mg BID | Factor Xa inhibitor |
| Advantages | No monitoring needed, can be used in renal failure with lower dose | |
| Disadvantages | Expensive, some hospitals may not have rapid access to reversal | |
| Half-life and reversal | 6–12 h | PCC, recombinant Xa (Andexxa) |
a Adjusted to PTT target of 60 s to 90 s.
b Adjusted to INR target of 2 to 3.
c Vitamin K–dependent proteins, including coagulation factors II, XII, IX, and XII; protein C; and protein S.
Although it has been previously suggested that anticoagulation alone may be sufficient for treatment of venous TOS, it has since become apparent that anywhere from 25% to 75% of patients experience unsustained symptom relief and various levels of long-term disability with this approach. The optimal duration of anticoagulation after SCV thrombosis is also undefined and cannot be extrapolated from protocols based on treatment of lower extremity venous thrombosis. Even lifelong anticoagulation may not prevent subsequent SCV rethrombosis, while placing healthy, young patients at risk for bleeding complications. Nonsurgical treatment of venous TOS would also require substantial limitations on upper extremity activity, in particular overhead positioning or heavy lifting, so is usually considered unacceptable for the typical patient population affected by this condition.
Interventional assessment and treatment
The main goals of treatment of venous TOS are to achieve complete relief of arm swelling symptoms, a return to unrestricted use of the affected extremity, and freedom from recurrent thrombosis without the need for lifelong anticoagulation. Catheter-based contrast venography remains the most effective means to definitively confirm or exclude the diagnosis of venous TOS and it allows for immediate initial treatment by catheter-directed thrombolysis. , , Pharmacomechanical thrombolysis can provide rapid resolution of the acute axillary-SCV thrombus and it is often successful in a 1-hour to 2 hour–long session, whereas previous approaches involved continuous thrombolytic agent infusion over a 24-hour to 48-hour period with monitoring in an intensive care setting ( Fig. 5 ). Upon follow-up imaging after successful thrombolysis, there is typically a persistent, focal, high-grade SCV stenosis at the costoclavicular space; this is not due to residual clot but represents the extramural and intramural SCV fibrosis caused by repetitive mechanical trauma. Balloon angioplasty (to a diameter of 10–12 mm) may improve the radiographic appearance of any residual SCV stenosis, but this is unlikely to be durable because the unaddressed mechanical compression of the vein and the residual scar tissue will inevitably result in SCV reocclusion. SCV balloon angioplasty, therefore, is useful to achieve a temporary improvement in venous flow and rapid resolution of arm swelling, but is generally not necessary or definitive. A strong recommendation is made against placement of stents in the SCV in patients with venous TOS in the absence of surgical decompression, because stents in this location are known to be at high risk for mechanical deformation that can cause rethrombosis and chronic pain from stent fracture, often within several months. , SCV stents thereby cause more problems than they resolve and can add a high level of complexity to any subsequent surgical treatment. In most patients, after thrombolysis the systemic anticoagulation is maintained to help prevent early rethrombosis and a plan for definitive surgical treatment is considered.
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