Subclavian vein thrombosis (SCVT) is a condition where a blood clot forms in the subclavian vein. SCVT can occur from multiple etiologies and is a potentially life-threatening pathology if not treated in a timely manner. SCVT occurs due to either a primary etiology or a secondary etiology. Primary thrombosis is further delineated as effort induced (Paget-Schroetter syndrome) or idiopathic (frequently associated with undiagnosed malignancy). Secondary subclavian vein thrombosis is associated with catheters or lines in the vein. While primary thrombosis is rare, the incidence of secondary thrombosis continues to rise as a consequence of complex cardiac devices and long term central venous catheters (CVC) placement in cancer patients. SCVT has high rates of acute mortality and long term disability without proper and timely treatment. Early diagnosis and treatment are essential in preventing fatal acute complications, such as pulmonary embolism and long term morbidity related to venous inflow restriction.
Causes of Primary SCVT
Causes of Secondary SCVT
The incidence of upper extremity deep vein thrombosis has been previously reported to be as high as ten percent of all cases of deep venous thrombosis. However, effort induced primary thrombosis is rare, occurring in 2 patients per 100,000 per year. Generally, effort induced primary thrombosis occurs in young, healthy, and athletic patients. The male: female ratio is approximately 2:1 male: female. While idiopathic thrombosis is associated with inherited thrombophilia, the precise incidence is unknown due to a lack of data. Interestingly, 25% to 30% of patients with unexplained upper extremity thrombosis will have an underlying malignancy. There have been contradictory studies regarding if oral contraceptives can increase the risk for SCVT.
The incidence of secondary subclavian thrombosis continues to increase with the use of advanced cardiac devices and chronic central venous catheters. Catheter-associated thrombosis is the cause of 93% of upper extremity thrombosis. The incidence is higher, with peripherally inserted catheters as compared to centrally inserted. Inappropriate position of the catheter tip can also contribute to increased thrombotic events.
Primary Thrombosis Etiology (Paget–von Schrötter syndrome)
Primary thrombosis is usually seen in healthy, young individuals. It is also referred to as spontaneous axillary subclavian vein thrombosis (ASVT) due to its unexpected presentation. Recent studies have shown that the syndrome can affect all ages. In the past, the syndrome was known as effort-induced thrombosis. Effort-induced thrombosis was used to describe the disease as unexpected thrombosis occurring after strenuous or repetitive use of the upper extremity on the affected side.
The pathophysiology of the disease is contributed to many factors. First of all, it is important to understand the anatomy of the structures of the thoracic outlet and the venous system. The clavicle is superior to the thoracic border of the subclavian vein, and the first rib is located inferior to the subclavian vein. The anterior scalene muscle is located laterally to the vein, and the costoclavicular ligament is located medially. The subclavian vein passes through the thoracic outlet prior to reaching the internal jugular vein. Changes in slight anatomy can cause compression of the vein. When the arm abducts, the subclavian vein is compressed between the clavicle and the first rib. This results in the perfect setup for Virchow’s triad- endothelial cell damage, inflammation, scarring, hypercoagulability, and stasis of blood. The costoclavicular ligament is more commonly seen inserting laterally in patients with thrombosis resulting in the compression of the subclavian vein. Repetitive movements in the area that includes the subclavius and anterior scalene muscles also contribute to venous compression and injury. Other anatomical changes that can increase the risk of thrombosis are the abnormal insertion of the first rib, congenital fiber-muscular bands, or narrowing of the costoclavicular space. In addition, any hematologic pathologies that many coexist can contribute to thromboses, such as factor V Leiden mutation, protein C deficiency, or anti-thrombin III. Idiopathic primary thrombosis is frequently linked to an occult malignancy or coagulation abnormality.
Catheter-induced Subclavian Vein Thrombosis
Placing pacemakers and central catheters will alter the venous blood flow and create turbulence in the vein. This will start the cascade of platelet aggregation, the release of procoagulants, and, ultimately, fibrin deposition. A thrombus forms that will reduce the size of the vein, ultimately leading to total vessel occlusion. In patients with risk factors for thrombus, such as cancer, immobility, and hemophilic disorders, this will be an additional contributing factor.
Patients with SCVT will present with complaints of upper extremity or neck discomfort or pain. They may describe it as a "feeling of vague fullness" and possible swelling in the affected upper extremity. Patients with primary effort induced SCVT can present as typically healthy, teenage to 40 years old, males more often than females. History may reveal recent strenuous or repetitive movements of the extremity, whereas idiopathic SCVT will not have any strenuous activity history. A patient's complaints and findings in secondary SCVT are similar, but the presence of a catheter or device lead or history of trauma will be present. The loss of function of the catheter is also frequently noted.
Physical findings will reveal supraclavicular fullness, a palpable mass, changes of color of the extremity, and Urschel's sign (dilation of the collateral veins in the anterior chest wall). The severity of symptoms depends on the degree of venous obstruction. Early in the disease process, patients will complain of mild discomfort. As the process evolves, more prominent signs and symptoms will appear.
An active, healthy individual who presents with a new onset of upper extremity swelling should be considered for SCVT. Ultrasound is the preferred diagnostic tool with a specificity of 96% and a sensitivity of 97%. The diagnosis can be made with computed tomography, magnetic resonance imaging (MRI), and direct venography when the diagnosis is uncertain, but there are disadvantages. Disadvantages of these other diagnostic modalities include expense, radiation exposure, use of intravenous contrast, and delay in diagnosis. Workup for hypercoagulable states should be reserved for patients with idiopathic primary SCVT.
The primary treatment for SCVT is anticoagulation. Within the first 14 days of onset of primary SCVT, pharmacologic thrombolysis or mechanical thrombolysis both yield excellent results. Anticoagulation with low molecular weight heparin (LMWH), warfarin, or direct oral anticoagulants (DOAC) for a period of 3-6 months is recommended. Patients with effort induced SCVT and recurring symptoms will likely benefit from surgery by surgical decompression of the thoracic outlet or resection of the first rib and associated muscles and ligaments depending on the anatomy. Angioplasty and stenting of the vessel can also be done for the management of the thrombosis, but is more invasive and typically reserved for recurrent events.
Idiopathic primary SCVT without evidence of malignancy is treated with anticoagulation for 3-6 months. SCVT associated with malignancy is treated with LMWH until the malignancy is cured or in remission.
Management of catheter-related SCVT varies. If the catheter can be removed, and there is a low risk of embolization and no prothrombotic risk, the catheter should be removed, and then there is no need for anticoagulation therapy. If there is a high risk of embolization, anticoagulant therapy should be initiated. Once the use of the long-term catheter is complete, the catheter must be removed, and anticoagulant treatment continued for at least 6 weeks after removal. If thrombosis occurs, and the catheter is required for therapy and still functional, then anticoagulation should be initiated immediately and continued for at least 3 months after the chronic catheter is removed. There is no consensus on the benefits of the use of compression sleeves.
Differential diagnoses of subclavian vein thrombosis include:
Prognosis varies based upon risk factors for thrombosis and the percentage of occlusion of the vein. If untreated, residual venous obstruction in patients with Paget-Schroetter is present in 78%, with persistent symptoms. Disability occurs as a consequence of the thrombosis in 41% to 91% of cases. If treated appropriately with conservative measures or surgical intervention, the prognosis of effort induced SCVT is excellent.
The prognosis of idiopathic SCVT is dependent on the presence or absence of malignancy or thrombophilia. Cancer patients with SCVT have rates of complication as high as 50%. Complications of pulmonary embolism are about 9.2%, superior vena cava syndrome is 14.9%, and post-thrombotic syndrome is 26.4%. The 12-month mortality associated with SCVT and malignancy is reported as high as 40% secondary to the underlying disease (malignancy, multi-system disease) rather than direct complications of SCVT.
There is no consensus regarding prophylactic anticoagulation. More recent studies have shown little benefit for prophylactic treatment, however, the use of low molecular weight heparin in selected groups of patients may be worthwhile. Misplacement of the catheter tip in the superior vena cava should be identified and corrected. Left-sided catheter insertion should be avoided if possible. Patients should be educated on risk factors that may increase the risk of thrombosis, such as smoking, pregnancy, and obesity, to name a few.
If SCVT is diagnosed, anticoagulation must be started immediately. Doppler ultrasound is the first choice of diagnostic modality. If a patient has cancer, the patient must be treated with anticoagulation while being treated for active cancer. If the physical exam is suggestive of a thrombus in a patient with risk factors and the patient is complaining of chest pain, the patient should be started on anticoagulation right away if the testing modality is delayed due to the risk of pulmonary embolism. If chronic catheters are required, and SCVT is diagnosed, then anticoagulation must be continued for at least 3-6 months with close followup depending on the individual underlying risk factors.
If SCVT is suspected, it must be treated in a timely manner to prevent the dire consequences, such as pulmonary embolism or complete occlusion of the vessel. This is based on a good and detailed history and physical exam that can lead to decreased mortality. SCVT should be managed by a strong interprofessional team to include primary and emergency department clinicians, hematology, oncology, interventional radiology, and vascular surgery. Nurses and pharmacists should be part of the team as well. Collaboration and coordination within the team in the care of these patients will lead to better outcomes.
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