A 73-year-old man presented to the emergency department with right upper-extremity swelling. Initially he had diffuse muscle pain in the right shoulder, which he attributed to a viral syndrome. His medical history consisted of hypertension, gout, and benign prostatic hyperplasia. He had no history of venous thromboembolism and no family history of thrombophilia. The patient was up to date on his cancer screenings. He did not smoke and rarely drank alcohol. Outpatient medications included allopurinol, doxazosin, lisinopril, and hydrochlorothiazide.
Physical exam showed a well-developed man in no acute distress. He was afebrile with normal vital signs. Physical exam was remarkable for a swollen right upper extremity with erythema and slight induration in the more proximal region of the limb. The remainder of his exam was normal. Admission labs revealed a hemoglobin level of 12.8 g/dL, a white blood cell count of 8,000 cells/mm3, and a platelet count of 161,000 cells/mm3. All of his chemistries were normal. An ultrasound of his right upper extremity revealed an occlusive to near-occlusive thrombus in his right axillary, subclavian, and basilic veins.
The patient was placed on IV heparin. He had a CT scan of his chest, abdomen, and pelvis that revealed no abnormalities besides the thrombus. He was switched to oral rivaroxaban and discharged home 2 days later. He received anticoagulation for a total of 6 months.
Upper-extremity deep venous thrombosis (DVT) refers to thrombosis of the internal jugular, brachiocephalic, brachial, subclavian, and/or axillary veins (1, 2). Usually the thrombotic process involves more than 1 venous segment, with the subclavian vein most frequently affected (3). The internal jugular vein, the brachiocephalic vein, and the basilic vein are additionally involved in up to 20% to 30% of these patients (1, 4). Upper-extremity DVT is far less common than lower-extremity DVT but still may account for as much as 10% of DVTs. The annual incidence of upper-extremity DVT is 0.4 to 1 case per 10,000 people (5) but may be increasing in frequency because of the use of indwelling central venous catheters as well as cardiac pacemakers and defibrillators. Compared to patients with lower-extremity DVT, upper-extremity DVT patients are typically younger, thinner, more likely to have a diagnosis of cancer, and less likely to have thrombophilia (1). Cancer is found in up to 40% of patients with upper-extremity DVT (6).
This condition can present with arm swelling, pain, and functional impairment; however, asymptomatic cases have been reported. Other clinical features such as visible collateral veins at the shoulder girdle or jugular distention are less frequent (1). Fewer than 50% of symptomatic patients have objectively confirmed upper-extremity DVT.
Potential complications include pulmonary embolism, which occurs in about 6% of patients with upper-extremity DVT, and postthrombotic syndrome, which occurs in about 5% of patients. Both complications are more common in lower-extremity DVT, occurring in 15% to 32% and 16% to 29% of such patients, respectively (5). Patients with catheter-associated DVT have a lower risk of post-thrombotic syndrome than those with primary cases (7). However, they have a higher risk of pulmonary embolism, especially compared to patients whose DVT is effort-related (8). A clot in the axillary or subclavian veins and residual thrombosis at 6 months are risks of post-thrombotic syndrome. Risk of recurrence at 12 months is lower with upper-extremity DVT, especially catheter-associated, than with lower-extremity DVT (1).
Twenty percent of cases of upper-extremity DVT are of primary etiology. This usually involves repeated microtrauma to the subclavian vein and surrounding structures due to anatomic abnormalities within the costoclavicular junction, which may result in inflammation, venous intimal hyperplasia, and fibrosis—known as the venous thoracic outlet syndrome (5).
About two-thirds of patients with primary upper-extremity DVT report strenuous activity involving force or abduction of the dominant arm, such as rowing, weight lifting, or playing tennis, before clot development. This is known as the Paget-Schroetter syndrome. The major risk is external compression of the neurovascular bundle at the thoracic outlet (9).
In most cases of primary upper-extremity DVT, the etiology is felt to be compression of the subclavian vein due to congenital narrowing of the space bounded by the clavicle, the first rib, the subclavian muscle tendon, and the costoclavicular ligament. Cervical ribs are not considered to be relevant (1, 9).
The other 80% of upper-extremity DVT cases are secondary, with causes including catheters; cancer; surgery, trauma, or immobilization by plaster casts; pregnancy; oral contraceptives; and estrogen. The most important risk factor is the presence of an indwelling central venous catheter (2, 6). About 50% of upper-extremity DVT patients have a central catheter present (10). Cancer patients with indwelling catheters are at particularly increased risk (11). Patients with implantation of permanent pacemaker leads and inherited thrombophilic disorders have been shown to also have an increased risk of catheter-associated thrombosis (12). The other major risk factor for secondary upper-extremity DVT is malignancy. Mechanisms include venous stasis due to immobilization, direct vein compression by the tumor itself, and cancer-induced prothrombotic factors (1). The risk is increased in patients with distant metastases (6). Ovarian carcinoma and lung adenocarcinoma carry higher risks of upper-extremity DVT, especially in the presence of indwelling catheters (13).
The clinical signs and symptoms of upper-extremity DVT are nonspecific. The diagnostic algorithms using clinical pretest probability and D-dimer have not been validated for upper-extremity DVT as they have for lower-extremity DVT, and thus imaging is needed (1). Compression ultrasonography is the imaging test of choice, but the proximal subclavian and brachiocephalic veins are hard to visualize because of overlying bony structures (5). Thrombosis is characterized by incomplete compressibility of the venous segment involved. MRI and CT scan should be considered as supplemental studies in cases with equivocal or negative ultrasound despite high clinical suspicion (5).
There is no evidence to recommend general screening for thrombophilia in patients with upper-extremity DVT (14). However, patients with unexplained upper-extremity DVT should undergo cancer screening in accordance with the recommendations for patients with lower-extremity DVT (15).
The American College of Chest Physicians issued new guidelines regarding treatment of upper-extremity DVT in January (16):
- In patients with acute upper-extremity DVT that involves the axillary or more proximal veins, we suggest anticoagulant therapy alone over thrombolysis (Grade 2C).
- In patients with upper-extremity DVT who undergo thrombolysis, we recommend the same intensity and duration of anticoagulant therapy as in patients with upper-extremity DVT who do not undergo thrombolysis (Grade 1B).
The American College of Chest Physicians' previous guidelines from 2012 offered additional specifics (17):
- In acute upper-extremity DVT in axillary or more proximal veins, parenteral anticoagulation (low-molecular-weight heparin [LMWH], fondaparinux, or IV or subcutaneous unfractionated heparin [UFH]) is recommended over no acute treatment (Grade 1B). LMWH or fondaparinux is suggested over IV UFH (Grade 2C) and over subcutaneous UFH (Grade 2B).
- For patients with upper-extremity DVT associated with a central venous catheter, it is suggested that the catheter should not be removed if it is functional and there is ongoing need for it (Grade 2C). If the catheter is not removed, it is recommended that anticoagulation continue as long as the catheter remains in patients with cancer (Grade 1C) and the same is suggested in patients without cancer (Grade 2C). If the catheter is removed, 3 months of anticoagulation is recommended over longer treatment in patients with no cancer (Grade 1B) and suggested in patients with cancer (Grade 2C).
- If upper-extremity DVT is not associated with a catheter or cancer, 3 months of anticoagulation is recommended over longer duration of therapy (Grade 1B).
Randomized trials of thrombolysis for upper-extremity DVT are lacking and severe postthrombotic syndrome is not typically seen, so thrombolysis is not usually recommended (4). It may be considered in selected patients with acute thrombosis of the arm veins and extensive swelling of the upper arm with severe symptoms who are at low risk of bleeding (1, 17). Mechanical catheter interventions (aspiration, fragmentation, thrombectomy, balloon angioplasty, or stenting) can be considered in patients with persistent, severe symptoms (18).
Surgical treatment involves decompression of the venous thoracic outlet. It includes resection of parts of the clavicle and the first rib, supplanted by circumferential venolysis and scalenectomy (1, 2). The procedure should be reserved for those with persistent severe manifestations despite anticoagulation and thrombolytic therapy (1, 17).