Venous TOS resulting in effort thrombosis of the subclavian vein (Paget-Schroetter syndrome) is a relatively uncommon condition, but it is probably the most frequently encountered vascular disorder in young competitive athletes. Understanding this condition is particularly important since delayed diagnosis and/or incomplete treatment of effort thrombosis can lead to persistent symptoms and impose significant limitations, as well as prevent further participation in particular kinds of work, sports and recreational activities.
With early recognition, proper initial treatment, and prompt referral for definitive surgery, most individuals — including competitive athletes — can return to previous levels of activity within several months.
Important features of venous TOS include the following:
- Most frequently occurs in individuals between 15 and 35 years of age, with an equal distribution between males and females.
- Most patients are otherwise healthy and physically active.
- Many patients are engaged in vigorous use of the upper extremities in work-related or recreational activities that involve repetitive overhead use and/or heavy lifting. (See story of venous TOS patient treated by Robert Thompson, MD, at The Washington University Center for Thoracic Outlet Syndrome at Barnes-Jewish Hospital)
History and Symptoms of Venous TOS
Although there are no specific disease conditions that predispose an individual to the development of venous TOS, the following should be sought as potential contributing factors:
- A history of a previous deep vein thrombosis (DVT)
- Oral contraceptive use
- Previous placement of an indwelling central venous catheter
- Known hypercoagulability (excessive blood clotting) disorder
The most frequent symptoms experienced by patients with venous TOS include:
- Sudden spontaneous onset of arm and hand swelling, often involving the entire arm and beginning at the level of the shoulder (the magnitude of swelling is usually quite substantial, with the diameter of the affected extremity increased as much as twice that of the opposite side)
- Bluish or reddish discoloration of the arm and hand, which may be more pronounced when the hand is in a dependent position
- Fatigue, tightness, heaviness, and pain in the arm, especially with use or overhead positioning
- Visible distention of subcutaneous veins in the upper arm, around the shoulder, or in the upper anterior chest wall
- General fatigue, shortness of breath with exertion and chest pain, all suggestive of the possibility of pulmonary embolism, may also be present
Current estimates suggest that pulmonary embolism occurs in approximately 10% of patients with effort thrombosis. Although uncommon, occasionally a patient may have primary symptoms of pulmonary embolism and no or minimal arm swelling, in whom a negative evaluation for lower extremity DVT has led to a broader examination that has subsequently revealed subclavian vein thrombosis.
In contrast to the effort thrombosis syndrome, some patients with venous TOS may have a more protracted history of arm swelling, fatigue, heaviness, and pain that occurs only on an intermittent basis, especially following vigorous use of the arm. Such patients may have non-thrombotic positional obstruction of the subclavian vein at the level of the first rib, which has not yet evolved to produce axillary-subclavian vein thrombosis.
Another subset of patients may have a chronic history of upper extremity venous insufficiency that has caused persistent or progressive limitations in activity over a period of many months to several years. These individuals are often found to have had previous axillary-subclavian vein thrombosis that was unrecognized and/or untreated.
In patients with effort thrombosis or more chronic presentations of venous TOS, it is helpful to elicit any symptoms that may also suggest the presence of neurogenic TOS, such as pain, numbness, and/or tingling in the hand and fingers. Experts with the Thoracic Outlet Syndrome Center at Washington University and Barnes-Jewish Hospital estimate that up to 20% of patients with venous TOS exhibit symptoms that are attributable to some degree of coexisting neurogenic TOS.
Physical examination in patients suspected to have venous TOS is directed towards:
- Clarifying the extent and magnitude of arm swelling
- Identifying any signs of coexisting neurogenic or arterial TOS
- Excluding conditions that might otherwise explain the presenting symptoms
Components of the physical exam include:
- The distribution of arm swelling is determined visually, and comparative measurements of arm circumference may be made with the opposite arm to gain insight into the magnitude of swelling
- The upper extremity is examined for overt hand edema, as this may suggest lymphedema or chronic regional pain syndrome (CRPS) rather than venous obstruction
- The upper medial arm is palpated for any evidence of a palpable cord, which may be associated with extension of thrombus into the axillary or basilic veins of the upper arm
- The arm and hand are inspected for discoloration in a dependent position and for any changes that occur with arm elevation
- Most patients with venous TOS exhibit distention of subcutaneous veins around the shoulder and upper chest wall, which can be easily compared to the opposite side
- Examination to elicit signs of brachial plexus compression (following that described in the section on neurogenic TOS)
In the vast majority of situations, the clinical diagnosis of axillary-subclavian vein effort thrombosis is apparent from the stereotypical history and physical examination findings.
Vascular Laboratory Tests
There remains some debate over the best diagnostic studies to perform in confirming or excluding the possibility of effort thrombosis. Duplex imaging studies have a false-negative rate as high as 30% for effort thrombosis and are thereby not sufficiently accurate to exclude the diagnosis of venous TOS if negative.
Duplex studies are nonetheless of value if they are positive for the presence of axillary-subclavian vein obstruction, helping to confirm the clinical diagnosis and leading to further testing and treatment.
Blood Coagulation Testing
Laboratory testing in patients with upper extremity DVT typically consists of hematological studies to detect any underlying coagulation disorders. Although venous TOS with effort thrombosis is considered to be a “mechanical” problem and unrelated to any increased propensity toward thrombosis, it has been reported that more than 50% of patients with venous TOS exhibit abnormalities in coagulation tests.
Since the presence of a coexisting hypercoagulable condition (thrombophilia or the propensity to develop blood clots) may influence subsequent patient management (e.g., the potential need for long-term anticoagulation), it is useful to obtain these types of studies in the setting of the initial diagnostic evaluation or in follow-up. The following studies are those most frequently performed:
||Type of Test/Assay
||Functional and/or antigenic assay
||Functional and/or antigenic assay
|Antithrombin III level*
||Functional and/or antigenic assay
|Total plasma homocysteine
|Prothrombin mutation (G20210A)
|Factor V Leiden mutation (G1691A)
|PAI-1 mutation (4G/5G)
|MTHFR mutation (C677T)
|Presence of anticardiolipin antibodies, IgG and IgM
||Enzyme-linked immunosorbent assay
|Presence of lupus anticoagulant
||Enzyme-linked immunosorbent assay
Abbreviations: MTHFR = methyltetrahydrofolate reductase; PAI = plasminogen activator inhibitor-1.
*Assays that are altered by anticoagulation treatment (warfarin, heparin, argatroban, etc) or by recent thrombolytic therapy (tissue plasminogen activator). Blood coagulation studies are performed either prior to or at least 2 weeks after the completion of treatment with anticoagulant medications and thrombolysis.
Contrast-enhanced imaging studies such as contrast-enhanced computed tomography (CT) or magnetic resonance (MR) angiography are required to confirm the clinical suspicion of axillary-subclavian vein thrombosis or venous TOS, and should be performed without delay in most clinical situations.
Since CT or MR venography provides more anatomic information than venous Duplex imaging, these studies can also be used to exclude the diagnosis of venous TOS when negative.
The definitive diagnosis of axillary-subclavian vein effort thrombosis and venous TOS requires direct catheter-directed contrast venography performed by percutaneous access through a vein in the affected arm.
Direct venography provides the most complete anatomic information regarding the site and extent of thrombosis and allows the most definitive evaluation of the status of the collateral veins. Direct venography is also required to undertake catheter-based venous thrombolysis, which is the preferred initial step in treatment of almost all patients who have effort thrombosis.
Taking all of these factors into consideration, specialists at the Thoracic Outlet Syndrome Center believe the most practical, efficient, and cost-effective approach to evaluating the patient with suspected effort thrombosis is to go directly to catheter-based venography, rather than utilize Duplex studies or other non-invasive imaging tests.
In the absence of any contraindications, once the diagnosis of axillary-subclavian vein effort thrombosis is suspected almost all patients should be anticoagulated with intravenous or subcutaneous heparin.
This treatment can be done while additional diagnostic studies are being performed or before patient transfer from one hospital to another, and it is important to help prevent the extension of thrombus within the axillary and subclavian veins. Treatment with an anti-platelet agent, such as aspirin or clopidogrel (Plavix), is often included. In the event that subsequent diagnostic studies demonstrate no evidence of axillary-subclavian vein thrombosis or venous TOS, treatment with anticoagulant and antiplatelet medications is discontinued and alternative diagnostic evaluation is undertaken.
Thrombolysis is a treatment option usually performed at the time of the initial venogram. It involves the localized administration of a protein that breaks down an existing clot, thereby restoring relatively normal flow within the blood vessel and allowing better visualization of any remaining stenosis. After completion of a catheter-directed venogram to verify the diagnosis of subclavian vein occlusion, thrombolytic therapy should be strongly considered in the same setting.
Thrombolysis is not advised as a treatment option in the following situations:
- Within 2 weeks of major surgery or trauma
- In the presence of active internal hemorrhage
- A history of stroke or cerebral hemorrhage, brain tumor or vascular malformation
- Uncontrolled hypertension
Venous thrombolysis has been traditionally performed by continuous infusion of the thrombolytic drug (e.g., tissue plasminogen activator, or TPA) directly into a catheter placed within the axillary-subclavian vein at the time of the initial venogram.
Infusion of the thrombolytic drug is continued for a period of 24 to48 hours, with repeat venograms performed at follow-up intervals until a maximum effect is achieved. Because of the risks of bleeding, monitoring in an acute-care setting (e.g., intermediate care or intensive care unit) for several days is required.
Thrombolysis is now usually performed with catheter-based “pharmaco-mechanical” thrombectomy, in which a mechanical device on the tip of the catheter is used to rapidly break up the clot, along with localized infusion of a much smaller amount of thrombolytic agent. The great advantage of this approach is that it can usually be completed in a single stage, often within several hours, thereby avoiding a long stay in a monitored hospital setting. The goal of thrombolysis is to clear any fresh or recent clot from the axillary-subclavian and collateral veins.
After thrombolysis, attempts to dilate residual subclavian vein stenoses using balloon angioplasty are usually unsuccessful, and even when improvement is obtained it is usually short-lived. We therefore rarely recommend the use of balloon angioplasty for subclavian vein stenosis following thrombolysis.
There is also a large amount of evidence demonstrating that vascular stents should not be placed in the subclavian vein, at least prior to surgical decompression, because of an inevitably high rate of failure.
After thrombolysis, the patient should remain on systemic anticoagulation (intravenous unfractionated heparin or subcutaneous low molecular weight heparin) and referred for surgical management.
Because effort thrombosis is caused by repetitive mechanical compression of the vein rather than a disorder of blood clotting, many recommend lifelong anticoagulation in the absence of definitive surgical treatment of the anatomic cause.
Traditionally, conservative treatment of subclavian vein effort thrombosis has consisted of:
- Chronic anticoagulation
- Intermittent arm elevation
- Long-term restrictions in arm activity
- The use of compression sleeves
With conservative management and observational care, there is a considerable likelihood of recurrent thrombosis despite long-term anticoagulation, with published estimates ranging from 50-70%.
At present, specialists at the Thoracic Outlet Syndrome Center at Washington University and Barnes-Jewish Hospital recommend observational care primarily in patients not considered to be suitable candidates for surgery or for sedentary elderly patients.
Surgery for Venous TOS
Indications for Surgery
Surgical treatment provides definitive management for effort thrombosis and venous TOS and should be considered in almost all patients with this condition.
Operative treatment is centered upon two goals:
(1) Decompression of the subclavian vein and collateral venous pathways through the thoracic outlet, by removal of the first rib and associated scalene and subclavius muscles
(2) Restoration and maintenance of normal blood flow through the subclavian vein, by removing constricting scar tissue from around the vein, by balloon angioplasty, or by direct venous reconstruction when necessary
Thoracic outlet decompression for venous TOS can be performed through the following surgical approaches:
- Infraclavicular (subclavicular)
- Combinations of these incisions
Based on extensive experience with venous TOS, specialists at the Washington University Center for TOS use an anterior paraclavicular approach that involves incisions above and below the clavicle.
This approach permits more complete first rib resection and more thorough venous decompression that can be obtained through any of the alternative approaches, and it allows completion of these steps to be accomplished during a single operative procedure and hospital stay.
The vast majority of patients with recent axillary-subclavian vein effort thrombosis are excellent candidates for surgical treatment, particularly within the first several weeks of undergoing successful thrombolytic therapy. However, some patients may be considered to be unsuitable candidates for surgical treatment. This judgment depends in large part upon the surgical experience available and the surgical approaches to venous TOS preferentially used in a particular center.
Specialists at the Washington University Center for Thoracic Outlet Syndrome at Barnes-Jewish Hospital take a unique and comprehensive approach for the surgical treatment of venous TOS and find few patients unsuitable candidates for treatment of symptomatic venous TOS.
The first step in paraclavicular thoracic outlet decompression for venous TOS is performed through a supraclavicular incision in the front of the neck, parallel to and just above the clavicle, similar to that used for supraclavicular decompression in neurogenic TOS. Through this approach, the same steps are taken, including mobilization of the scalene fat pad, scalenectomy and brachial plexus neurolysis, and division of the posterior portion of the first rib. The anterior portion of the first rib is not yet divided at this point in the procedure.
A second (infraclavicular) incision is then made parallel to and underneath the clavicle, beginning near the edge of the sternum. The upper and middle portions of the pectoralis major muscle are spread apart without dividing the muscle, and the anterior portion of the first rib is exposed. The intercostal muscles attaching to the lower side of the first rib are divided, followed by division of the subclavius muscle and costoclavicular ligament. The first rib is then traced to its attachment with the sternum, where any additional attachments are divided and the rib is divided. The entire first rib is then removed as a single specimen. The remaining segment of the subclavius muscle is then resected from underneath the clavicle.
Subclavian Vein Reconstruction
The two incisions made during paraclavicular decompression, as well as the removal of the entire first rib, allow excellent exposure for dissection of the subclavian vein. Through the infraclavicular incision, the axillary vein is first identified just below the clavicle and traced underneath the area occupied by the subclavius muscle, where it becomes the subclavian vein. The subclavian vein is exposed through this incision, and through the supraclavicular incision, where it is traced to its junction with the internal jugular vein to form the innominate vein.
Throughout this stage of the operation, fibrous scar tissue is removed from around the axillary-subclavian vein (“external venolysis”), and the vein is observed for any areas of constriction and stenosis, as well as areas that have expanded to a normal caliber. The subclavian vein is further assessed by palpation for areas of wall thickening or obvious obstruction, or areas that fail to fill with venous blood after manual compression.
In the event that the entire axillary-subclavian vein segment appears to have expanded to a normal size following external venolysis, no further reconstruction is performed. This is followed by an intraoperative venogram to ensure that the vein is widely patent and that there is no residual stenosis not evident by direct inspection. When inspection of the axillary or subclavian vein exhibits an obvious stenosis or occlusion despite external venolysis, or if an intraoperative venogram reveals an otherwise undetected stenosis, direct venous reconstruction is performed.
For direct venous reconstruction, the patient is anticoagulated with intravenous heparin and the axillary, internal jugular, and innominate veins are clamped. An opening is made in the axillary or subclavian vein just beyond the site of stenosis and carried along the length of the vein into the innominate vein beyond the stenosis. Any recent thrombus present within the subclavian vein is removed and the inside surface and wall of the vein are inspected further.
If the inside surface of the subclavian vein is smooth and free of chronic thrombus or severe wall thickening, the vein repair is completed with a wide patch angioplasty. In contrast, if the inside surface of the subclavian vein is ulcerated or the wall is severely thickening with chronic thrombus or fibrosis, then the affected segment of subclavian vein is excised and a bypass graft replacement is performed.
For the purposes of subclavian vein reconstruction (either patch angioplasty or bypass graft replacement), a segment of the saphenous vein, a superficial vein from the upper leg, is often used. However, the saphenous vein is usually too small to match the size of the subclavian vein and additional modifications are required if this is to be used for creation of a suitable bypass graft. Over the past several years, for these purposes we have more frequently selected use of a segment of cryopreserved femoral vein (a cadaver vein harvested from an organ transplant donor that is processed and stored frozen). This provides a vein replacement material that can be handled in a similar fashion to normal veins and is readily available in any size needed, and its use avoids the leg incision that would otherwise be needed for saphenous vein harvesting.
Completion VenographyAfter completion of subclavian vein external venolysis or direct venous reconstruction, the affected arm is repositioned on the operating table in preparation for an intraoperative venogram. Although this step appears to be often omitted by others, specialists at the Thoracic Outlet Syndrome Center at Washington University and Barnes-Jewish Hospital believe that completion venography is an important aspect of the operation that ensures the most optimal technical result has been obtained by the surgical procedure (and to allow any defects to be corrected at the same time). The small vein at the wrist is generally used for contrast injection, with intraoperative fluoroscopy to obtain high-quality X-ray images.
Use of Arteriovenous Fistulas
When direct reconstruction of the axillary or subclavian veins has been performed, there is always concern that the surgical manipulation may make the vein more prone to develop thrombosis in the early postoperative period, as well as during the first few weeks of healing. To limit this potential, for many years we have used creation of an adjunctive arteriovenous fistula (AVF) to help increase venous blood flow through the reconstructed vein. This type of AVF is created by attaching the small vein in the wrist to the side of the radial artery, establishing a “short-circuit” path for arterial blood to flow into the venous system.
Patients with a temporary AVF that has been created at the time of an operation for venous TOS are brought back to the outpatient operating room at 12 weeks after the initial operation, and the AVF is ligated with the patient under local anesthesia. In most cases, we also perform a follow-up venogram at the same time, to evaluate the final outcome of axillary-subclavian reconstruction.
Alternative Surgical Approaches
The principal alternative surgical approach to the treatment of venous TOS is transaxillary first rib resection. As in treatment for neurogenic TOS, this approach typically involves partial resection of the first rib and division of its scalene muscle attachments. Because it is not feasible to fully expose or control the subclavian vein from the transaxillary approach, direct evaluation and/or reconstruction of the subclavian vein is not performed. Rather, transaxillary first rib resection is usually coupled with the subsequent use of intraoperative or postoperative venography and performance of balloon angioplasty and/or stent placement to deal with any residual stenosis in the subclavian vein. Current estimates indicate that 40-50% of patients will demonstrate a residual subclavian vein stenosis requiring balloon angioplasty, even several weeks after first rib resection. Because these lesions are typically composed of dense scar tissue around and within the wall of the vein, balloon angioplasty may be relatively ineffective in this setting. Although placement of subclavian vein stents may be considered in this situation, the long-term effectiveness of stents in this position is limited. Long-term anticoagulation may therefore need to be considered in an effort to reduce the potential for recurrent venous thrombosis. For these reasons, we prefer more direct and thorough approaches to the management of patients with venous TOS.
Potential Complications of Surgery
The potential complications of surgical treatment for venous TOS are the same as those described in the previous section on neurogenic TOS. Several additional potential complications that are unique to operations for venous TOS include:
- Residual subclavian vein obstruction or early rethrombosis
- Postoperative bleeding
- Arm swelling and signs of venous congestion
- Late subclavian vein obstruction or thrombosis
Expected Outcomes of Surgery
For patients undergoing surgical treatment for venous TOS, recovery is similar to those undergoing surgery for neurogenic TOS.
Patients are generally kept from returning to work or school for approximately 4 to 6 weeks after surgery, to allow sufficient time for recovery from the operation and to make satisfactory progress with physical therapy. Some patients may require a longer period of recovery before returning to work, depending on their preoperative levels of symptoms, pre-existing limitations and restrictions, and the nature of their work activities.
Some may return to limited activities earlier, particularly if their work or school activities are relatively sedentary.
Most patients can drive within 2 to 3 weeks of the operation, but in some this can aggravate neck muscle spasm.
Excessive activity in patients who return to work or other activities too early can lead to flares of neck and back muscle spasm, neurogenic symptoms, and even more prolonged recovery.
Recovery is typically complete within 3 months of the operation, and a full return to previous levels of function can usually be expected.
Patients who have had creation of an arteriovenous fistula in the wrist at the time of the original operation are re-examined at approximately 6 and 12 weeks after surgery. If there is still open flow through the AVF, the patient is brought to the operating room for a brief operation to perform a final venogram (and possible balloon angioplasty) and to ligate the AVF. These procedures are performed with the patient under local anesthesia in the outpatient setting with complete recovery within 1 to 2 days, after which full activity can be resumed.
Patients undergoing surgery for venous TOS are typically maintained on anticoagulation with warfarin (Coumadin) and clopidogrel (Plavix) for approximately 12 weeks after surgery. Our office monitors the dose requirements by periodic measurements of the INR and arranges dose-adjustments with the patient as needed. In most patients anticoagulation is thereafter discontinued 12 weeks after surgery.