Subclavian Vein Thrombosis

The subclavian vein courses over the first rib and posterior to the clavicle; the artery lies superior and posterior to the vein (see the image below). 

During long-term venous catheterization of the subclavian vein and internal jugular vein in cancer patients, the risks of complications appear to be similar. However, for short-term catheterization, subclavian vein catheterization is recommended because of the decreased risks of thrombotic complications and catheter colonization by skin flora. For patients requiring hemodialysis, the femoral and internal jugular veins appear to have similar thrombotic complications. However, the risk of mechanical complications via the internal jugular vein appear to be higher. The subclavian vein should be avoided for both long- and short-term hemodialysis because the risk of thrombosis is very high.[4]

Differentiating catheter-associated subclavian vein thrombosis and Paget–von Schrötter syndrome is important because they appear to have different natural histories.

Paget–von Schrötter syndrome

This syndrome sometimes is referred to as spontaneous ASVT to express the usually dramatic unexpected presentation of the disorder in otherwise healthy, generally young individuals.[5] Over the past few decades, there has been growing recognition that the disorder can occur equally in both sexes and can affect all age groups. In the 1960s, the term effort-induced thrombosis was applied to this disease to acknowledge that it often follows unusually strenuous use of the arm or shoulder on the affected side.

The pathophysiology of effort-induced thrombosis is multifactorial. It involves compressive changes in the vessel wall, stasis of blood, and hypercoagulability. External compression of the axillary-subclavian vein has been suggested to contribute to the stasis of blood that engenders thrombosis. The factors that cause external compression include the following:

• Anomalous subclavius or scalenus anterior, long transverse process of cervical spine, cervical rib, abnormal insertion of the first rib, congenital fibromuscular bands, or narrowing of the costoclavicular space from depression of the shoulder
• Stress from exercise temporarily causing hypercoagulability
• Repetitive shoulder-arm motion causing microscopic intimal tears in the vessel wall

These factors, taken together, satisfy the classic Virchow triad for thrombosis. Furthermore, coexistent hematologic abnormalities that can contribute to thrombosis include protein C deficiency, antithrombin III deficiency, factor V Leiden mutation, and prothrombin 20210A mutation.

Catheter-induced subclavian vein thrombosis

Introducing catheters and transvenous pacemakers in to the subclavian vein alters the venous flow and increases turbulence. This results in platelet aggregation, release of procoagulants, and, ultimately, fibrin deposition. This causes a further reduction in the lumen of the vessel due to thrombus formation, which eventually culminates in total vessel occlusion. Intravenous (IV) medications and even parenteral nutrition have been known to cause thrombophlebitis. In patients with cancer, an additional contributing factor is that the tumor may generate procoagulant factors, predisposing to thrombosis at sites remote from the tumor.

The primary etiology is referred to as effort-induced thrombosis or Paget–von Schrötter syndrome. It usually results from the excessive use of the involved arm by predisposed individuals. The secondary etiology is subclavian vein catheterization, especially in patients with cancer. (For detailed descriptions of catheterization techniques, see Central Venous Access via Infraclavicular (Subclavian) Approach to Subclavian Vein and Central Venous Access via Supraclavicular Approach to Subclavian Vein.)

Other causes include transvenous pacemakers, factor V Leiden mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, and prothrombin 20210A mutation. Long-term parenteral nutrition[6] and use of hemodialysis catheters[7] account for some cases of subclavian vein thrombosis. Trauma is only rarely associated with this syndrome.

In a few cases, the diagnosis remains unknown. However, routine follow-up with these patients has revealed the development of lung cancer within 1 year of follow-up. The most common lung malignancy associated with subclavian thrombosis has been the Pancoast tumor.

Before 1967, thrombosis of the axillary or subclavian vein accounted for 1-2% of all cases of deep vein thrombosis (DVT). Since then, the incidence has risen as a consequence of more frequent use of central venous access for multiple clinical conditions. Among patients with effort-induced thrombosis with subclavian vein stenosis, the thrombosis occurs in the dominant arm in 80% of cases.

Case fatality rates for untreated ASVT-related pulmonary embolism (PE) may be as high as 10%, a figure comparable to that seen with PE originating from the lower extremity. The long-term consequences of venous occlusion cause substantial morbidity related to persistent pain and swelling for protracted periods. These symptoms occasionally are severe and can be exacerbated by physical activity, particularly with extended use of the affected arm. Consequently, this syndrome can lead to occupational disability and can adversely impact the patient's quality of life.

Conservative treatment consisting of bed rest, limb elevation, and anticoagulation is associated with a worse outcome. Some reports suggest that as many as 74% of patients treated with these conservative measures have residual disability as compared with those who are treated with thrombolysis.

With advances in endovascular technology, there is more supporting evidence that these techniques are the modality of choice in the management of a patient with upper-extremity thrombosis. Anticoagulation or thrombolytic therapy alone has proved inadequate. Today, both benign and malignant causes of upper-extremity thrombosis can be managed with endovascular stenting. This technique allows much faster recovery while giving rise to less morbidity and fewer complications in the long run.[8]

A study by Mahmoud et al reported acceptable intermediate-term results for the treatment of Paget-Schrötter syndrome with a three-stage approach that included early thrombus removal, thoracoscopic first-rib resection, and postoperative venous balloon angioplasty.[9]

Patients may describe a history of trauma or, more frequently, strenuous use of the arm (>50% of cases). Common precipitating activities involve repeated hyperabduction and external rotation of the arm or backward and downward rotation of the shoulder. Causative activities may include participating in cricket, tennis, wrestling, lifting weights, water polo, gymnastics, baseball (see the image below), or chopping wood.

Because the symptoms of subclavian stenosis are fairly dramatic, most patients present promptly to the emergency department (ED), usually within 24 hours. They may report dull ache in the shoulder or axilla, and the pain often is worsened by activity. Conversely, rest and elevation often relieve the pain. Patients with catheter-associated axillary-subclavian vein thrombosis (ASVT) report similar symptoms of the ipsilateral arm or shoulder with the indwelling catheter.

Not all patients with subclavian vein thrombosis are symptomatic. Those with symptoms may present with mild-to-moderate nonpitting edema and mild cyanosis of the hands and fingers on the affected side. Dilatation of subcutaneous collateral veins may be present over the upper arm and chest. This later sign may be the only clue to ASVT in otherwise asymptomatic patients with catheter-related venous thrombosis.

In a few cases, in which the diagnosis was missed or delayed or the patient presented late, the thrombus may have extended to the superior vena cava (SVC). These patients show most features of the superior vena cava syndrome (SVCS), including face and neck swelling, periorbital edema, blurred vision, and some degree of facial cyanosis.[10]

Pulmonary embolism (PE) may occur in as many as 20-36% of patients. Stroke may occur as a manifestation of paradoxic embolism in the presence of a patent foramen ovale.

Other complications can include the following:

• Chronic venous insufficiency
• Phlegmasia cerulea dolens
• Superior vena cava syndrome
• Pulmonary hypertension
• Right-side heart failure
• Thoracic duct obstruction
• Chylous pleural or pericardial effusion
• Brachial plexopathy

Patients with suspected thrombophilia should have a full workup for hereditary causes. This should include the following:

• Lupus anticoagulant
• Factor V Leiden mutation
• Protein C
• Protein S
• Antithrombin III deficiency

If possible, blood for these tests should be drawn before anticoagulation is initiated because the coagulant factors listed above are reduced by heparin. When testing before anticoagulation is not possible, it may be performed 2 weeks after discontinuance of anticoagulants or factor X, which is equally affected by warfarin and can be drawn at the same time to serve as a benchmark for protein C and S.

Determine the complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen levels before beginning anticoagulants and thrombolytics. Monitor every 6 hours to prevent adverse effects of excessive anticoagulation.

Other tests to be performed should be relevant to the cause of the thrombosis.

The goal of the evaluation is objective verification of the presence of thrombus in the subclavian vein. The following imaging studies are useful for evaluation.

Chest radiography

Chest radiography is generally the initial radiologic modality of choice. It may be helpful in the detection of lesions that may be compressing the subclavian vein, such as a cervical rib or an apical lung mass. However, in most cases, the chest radiograph is a very insensitive test and is not useful in determining the cause of subclavian vein thrombosis. In addition, in many cases, the cervical rib is missed on the initial radiograph.

Ultrasonography

Ultrasonography (US)—real-time B-mode, duplex Doppler, or color Doppler—is being used with increasing frequency in the diagnosis of subclavian vein thrombosis. Compared with venography, duplex US has high specificity but relatively low sensitivity.

Subclavian vein thrombi not visualized by duplex US usually are either nonocclusive mural thrombi or thrombi located in the proximal part of the vein possibly shadowed by the clavicle and sternum. This modality is the test of choice for both screening and follow-up. If it yields negative results in the face of strong clinical suspicion, alternative modalities should be used.

Venography of subclavian vein

Traditionally, venography of the subclavian vein (see the images below) has been used for diagnosis of subclavian vein thrombosis, but it requires cannulation of a peripheral vein of the arm. Edema of the affected arm sometimes makes this difficult. Digital subtraction may allow the use of a smaller amount of contrast infused into a smaller vein. Venography carries the risk of contrast-induced adverse effects. The technique is only used when thrombosis is strongly suspected despite a negative US study.

Computed tomography

Computed tomography (CT) can detect subclavian stenosis, but it has not been studied thoroughly enough to allow determination of its specificity and sensitivity. CT is sometimes used when venography and magnetic resonance imaging (MRI) are not readily available. CT requires use of contrast. CT can readily image both the intrathoracic and extrathoracic structures with excellent resolution. Three-dimensional CT angiography (CTA) rivals MRI and venography in both resolution and sensitivity. CT can also detect thrombus and the presence of any extrinsic disease that may be causing the subclavian vein thrombosis.

Magnetic resonance imaging

MRI is highly specific for detecting subclavian vein thrombi, but its sensitivity (80% for thrombi that completely occlude the lumen and 0% for partially occlusive thrombi) is too low for this modality to be considered reliable in this setting.

In patients with effort-induced vein thrombosis of less than 2 weeks' duration, thrombolytic therapy is recommended. Chronic axillary-subclavian vein thrombosis (ASVT) rarely responds to thrombolytics and generally is better treated either conservatively with warfarin or, if symptoms are severe, with surgical bypass. A systematic review by Keir et al found first-rib resection followed by long-term anticoagulation to be the best treatment approach for chronic subclavian vein thrombosis.[11]

Surgery is rarely indicated for ASVT associated with central lines. 

Initial treatment of subclavian vein thrombosis consists of conservative management, which includes rest, elevation of the limb, and application of heat or warm compresses.

In a few patients who have minimal symptoms and no anatomic defects, physical therapy is the first component of treatment. Structured physical therapy may help the patient lose weight and loosens the adhesions at the site of obstruction. Physical therapy may also improve range of motion (ROM), decrease swelling, and help decrease pain.

The different natural histories of Paget–von Schrötter syndrome and catheter-induced subclavian vein thrombosis indicate different treatment protocols. Because large series of patients with this condition are lacking, the therapeutic approach to subclavian vein thrombosis is mainly anecdotal.

Anticoagulation

Unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) can maintain the patency of the venous collaterals and reduce the chance of propagation of the thrombus. In all cases, heparin therapy is followed by warfarin therapy, with a target international normalized ratio (INR) of 2-3.

Heparin is usually the initial therapy, followed by warfarin. LMWH has been used for both inpatient and outpatient therapy. Most studies have shown that LMWH is just as effective as UFH, but the former is associated with a significantly decreased incidence of venous thromboembolism.

Warfarin is continued for 6-9 months, and an INR of 2-3 is maintained. Patients who only receive inpatient heparin and are no longer on warfarin therapy are at risk for recurrence and long-term disability. Anticoagulation is required in all patients for a period of 6-9 months or longer, depending on the cause of the thoracic outlet syndrome. In some patients who also have hypercoagulable disorders, treatment is lifelong.

Levy et al, in a study involving 300 patients with upper-extremity deep vein thrombosis (DVT; including 161 with subclavian obstruction and 107 with axillary obstruction), concluded that in view of the low (2%) incidence of pulmonary embolism (PE) attributable to upper-extremity DVT, regardless of anticoagulant therapy, analysis of risks vs benefits does not favor routine anticoagulation in this setting.[12]

Paget–von Schrötter syndrome

Currently, most investigators favor using thrombolytic therapy to rapidly restore the patency of the vein. Thrombolytic therapy should be initiated within 5-7 days of venous thrombosis. Fortunately, this syndrome occurs in fairly young individuals who do not have multiple medical illnesses that may contraindicate thrombolytic therapy. Thrombolytic therapy is preferred to thrombectomy because it does not carry the risks of an operation and the possibility of an intimal tear related to the embolectomy catheter.

In some cases, therapy may involve diagnostic venography, followed by thrombolysis, followed by several weeks of anticoagulation. If symptoms recur, a repeat venography may be indicated, possibly followed by balloon dilatation with or without stenting of the subclavian vein, and more anticoagulation. (See the image below.) The desired INR is 2-3. The goal of therapy is to minimize the likelihood of significant symptoms of venous obstruction.

To perform catheter-directed thrombolysis, the catheter is embedded in the thrombus. Urokinase infusion is started with a loading dose of 250,000 IU, followed by 4000 IU for the first hour, and 1000 IU for the next 24 hours. Heparin is infused at a rate of 800 IU/hr. Monitoring is performed by maintaining a fibrinogen level of at least 80-100 mg/dL. If venous patency is assured, warfarin is maintained for 3-6 months.

The removal of urokinase from the US market forced interventional radiologists to adopt less clinically defined protocols using tissue plasminogen activator (tPA). As the clinical situation with thrombolytic agents evolves and other agents enter the market, flexibility in thrombolytic administration protocols will be paramount.

Catheter-associated subclavian vein thrombosis

Prophylaxis in patients undergoing chemotherapy may include giving a fixed 1-mg dose of warfarin sodium daily, beginning on day 3 before catheter placement. This has been shown to lower the incidence of thrombosis. Exercise caution in selecting patients for thrombolytic therapy because patients with catheter-associated subclavian thrombosis often have significant comorbidity.

Indications for surgical treatment include the following:

• Presence of an anatomic anomaly, such as an anomalous subclavius or scalenus anterior, congenital fibromuscular bands, or narrowing of the costoclavicular space from depression of the shoulder
• Rethrombosis of the vein after previous thrombolytic treatment
• Endoluminal stent placement to prevent stent fracture from compression against the first rib

Possible forms of surgical treatment include the following:

• Embolectomy
• Bypass
• First-rib resection via a transaxillary or supraclavicular approach
• Medial subtotal claviculectomy

Conventional approach

Preoperative evaluation

The purpose of the preoperative evaluation is to determine whether there is any known or unsuspected coexisting disease that should delay, modify, or preclude the operation. Obtain a history and physical examination to identify risk factors and warning signs of coexisting diseases. This information guides further direction and depth of study. Relevant laboratory tests include the following:

• Complete blood count (CBC)
• Serum electrolyte levels
• Urinalysis
• Chest radiography
• Electrocardiography (ECG)
• Clotting profile
• Crossmatch
• Stool examination for blood.

Consultations should include a general internal medicine physician and an anesthesiologist.

Procedure

A first-rib resection may be carried out via either the transaxillary route[13] or the supraclavicular route (though it has been suggested that an infraclavicular approach may have benefits[14] ). Typically, the transaxillary route is simpler and safer and offers cosmetic benefits. The procedure is described below.

The patient is placed in the lateral thoracotomy position with the arm elevated. A skin incision is made in the axillary hairline between the pectoralis major and the latissimus dorsi. The first rib is reached by blunt dissection in the axillary tunnel, with care taken to avoid the second intercostobrachial nerve.

The subclavian artery and vein are identified, and the subclavius tendon is divided. Then, the scalenus anterior is identified and divided at the point where it inserts onto the first rib, anterior to the artery.

At this point, a digital search is made for anomalous bands. They may originate from the C7 transverse process, from an incomplete cervical rib, or from the scalenus medius.

After any bands are divided, the scalenus medius and the intercostal muscle attachments are pushed off the first rib. When all the muscle fibers are cleared and the T1 nerve root is visualized and protected, the rib is divided and removed.

The wound is irrigated with saline to detect pneumothorax. If pneumothorax is present, it can be treated by inserting a small chest tube into the pleural space. The tube can be removed in the recovery room if the lung is fully expanded and no air leak is present.

Postoperative care

Pain relief is one of the most important aspects of postoperative care. Various forms of narcotics can be administered parenterally or by patient-controlled analgesia devices. The importance of adequate pain control cannot be overemphasized.

Vital signs should be closely monitored as per unit protocol, then every 4 hours for 24 hours, and then every shift. In most cases, a Foley catheter is not required. Administer 5% dextrose in lactated Ringer solution at a rate of 125 mL/hr, and keep the arm elevated.

If the operation is not complicated, routine postoperative laboratory tests are not required. The prothrombin time (PT) and activated partial thromboplastin time (aPTT) should be measured every 6 hours if heparin therapy is started.

Early mobilization is important, and discharge planning should begin at admission. Patients usually are discharged when they are medically stable, afebrile, tolerant of oral intake, ambulatory, and reasonably comfortable with the ongoing rehabilitation exercises.

Endovascular treatment

Angioplasty with stenting is an excellent way to maintain venous patency; though data and follow-up on this technique are limited. When the superior vena cava is also involved, current endovascular techniques allow for stenting of the vessel, which produces excellent results.

Suction thrombectomy with an AngioJet System (Possis Medical, Minneapolis, MN) is often used with thrombolysis when the thrombus is localized. The procedure can rapidly extract the thrombus and reduce both the dose and duration of thrombolytic therapy. Suction thrombectomy is most useful for patients who present early. Surgical thrombectomy is fast becoming the procedure of choice; it is a better alternative to simple anticoagulation.

Pharmacomechanical thrombectomy appears to be effective for early thrombus removal in patients with Paget–von Schrötter syndrome; subsequent thoracoscopic or open surgical decompression of the subclavian vein should be considered.[15]

Complications related to surgery include the following:

• Injury to the phrenic nerve
• Chronic pain
• Pneumothorax
• Arm swelling due to excessive dissection in the axilla
• Recurrence of symptoms
• Incomplete resection of the first rib

After surgery, it is important to have the patient enrolled in a physical therapy program. There is moderate pain after the procedure, which may take 5-10 days to subside. Physical therapy can help improve muscle function, enhance ROM of the arm, and prevent swelling of the ipsilateral arm.

Patients with subclavian vein thrombosis must be followed carefully to ensure that the condition does not recur. Patients with persistent symptoms and evidence of recurrence may require radiologic workup and, possibly, surgery.