Researchers have extensively studied deep vein thrombosis (DVT) of the lower extremities. With the increased use of central venous catheters, cardiac pacemakers/defibrillators, and peripherally inserted central catheter (PICC) lines. DVTs in the upper extremities have become more commonplace and require a heightened index of suspicion from clinicians. Patients can be otherwise asymptomatic but commonly present with limb swelling. The most serious complication associated with any DVT, including upper extremity DVT, is a pulmonary embolus (PE). Recognition and appropriate intervention may prevent significant patient morbidity and mortality.
Upper extremity DVT primarily involves brachial, axillary, and subclavian veins. The internal jugular veins and the more distal radial and ulnar veins are involved less frequently. There are 2 forms of upper extremity DVT: primary and secondary. The primary form is known as Paget-Schroetter syndrome (PSS) and typically occurs in the dominant arm of younger athletic patients involved in activities requiring excessive and repeated motion of the upper extremities such as wrestling, swimming, gymnastics, and sports involving repetitive ball throwing (i.e., football, baseball, and basketball). The secondary form occurs most commonly in patients with central venous catheterization or patients with malignancy.
Upper extremity DVTs currently comprise 5% to 10% of all DVTs with the incidence rising annually. The majority of patients have a central line, while PSS accounts for only 10% to 20% of cases. The rate of upper extremity DVT in all patients with central catheterization is between 14% to 23%. PE occurs in up to 6% of DVTs affecting the upper extremities compared to 15% to 30% in the lower extremities. Post-thrombotic syndrome occurs in less than 5% of DVTs in the upper extremities compared to greater than 50% in the lower extremities.
In the primary form (PSS), repeated motions of the upper extremity result in hypertrophy of the scalene muscles, which can compromise the neurovascular bundle as it exits the thorax between the cervical rib and surrounding musculature. Repeated compression of the subclavian vein results in venous stasis as well as perivenous microtrauma activating the intrinsic coagulation pathway with eventual thrombosis. In the secondary form, catheterization disrupts the endothelial lining and also activates a similar coagulation cascade. Additionally, congenital and acquired cases of coagulation disorders such as Factor V Leiden mutation or malignancy also increase the risk for upper extremity DVT.
A focused history and physical exam often reveal clinical findings suggestive of upper extremity DVT, which can then be confirmed with subsequent imaging studies. The majority of patients present only with limb swelling and arm discomfort. The onset and duration of limb swelling along with any previous history of DVT should be obtained. Patients may also complain of arm heaviness. The physical exam may also reveal limb erythema with visible veins across the chest and upper extremity (Urschel’s sign). Personal and family history of hypercoagulable disorders are relevant as well as if any prior central venous catheterization has been attempted. In the primary form (PSS), patients will present with a sudden onset of severe limb pain and swelling often in the dominant arm. These patients are younger and often participate in activities requiring excessive and repeated motions of the upper extremity (e.g., baseball pitcher). In all patients, distal pulses should be assessed. Limbs appearing pale, cool and mottled are at risk of ischemia. Any motor or sensory deficit should be noted, as these require emergency intervention.
A focused history and physical exam can reveal findings suspicious for DVT in the upper extremity. The best way to confirm a diagnosis is with compression duplex ultrasonography. This test has a sensitivity of 97% and specificity of 96% for the determination of DVT in the upper extremity and is often the test of choice. However, several other imaging modalities including magnetic resonance and computed tomographic venography are superior to ultrasonography, but their clinical use may be limited by high costs, radiation exposure, and/or availability. The sensitivity of compression duplex ultrasonography is 97%, which is lower than magnetic resonance venography (100%). However, it is non-invasive, less expensive and widely available, thus remains the test of choice to diagnose upper extremity DVT. Laboratory studies are not required for diagnosis, but a coagulation assay can be ordered in patients suspected of having a hypercoagulable condition. In patients with a low suspicion of upper extremity DVT, a d-dimer test can help rule it out. A patient with upper extremity DVT complicated by PE may present with chest pain and shortness of breath. ECG should be performed because it will most commonly demonstrate sinus tachycardia.
The treatment of upper extremity DVTs depends on the clinical presentation. The majority of patients present with limb swelling in the setting of central venous catheterization. The American College of Chest Physicians recommends that the clinician first determine the necessity of the line. If it is required (e.g., total peripheral nutrition), it should remain in place, and the patient should be started on anticoagulation therapy. If the line is not needed, it should be removed but only after completion of 3 to 5 days of anticoagulation therapy. In the hospital, patients can be bridged to warfarin with unfractionated heparin. Patients should continue on warfarin for 3 to 6 months after diagnosis. The role of novel oral anticoagulant agents (e.g., dabigatran) is under current investigation, but recent data from the Swedish national anticoagulation registry, (National Quality Registry for Atrial Fibrillation and Anticoagulation [AuriculA]) suggests that these drugs can be used for the treatment of upper extremity DVT with acceptable efficacy and safety.
In the case of PSS, the treatment course differs as it typically involves acute thrombosis. As such, patients develop significant pain and swelling requiring intravenous catheter-directed thrombolysis. This often resolves pain and swelling but does not treat the underlying etiology. Patients with PSS will, therefore, require urgent surgical intervention for first rib removal. This provides additional space in the thoracic outlet to prevent future compression of the neurovascular bundle.
Several clinical states may mimic limb swelling seen in upper extremity DVT. For instance, localized infection with cellulitis may result in venous congestion, which may appear similar to a DVT. Patients with cellulitis may have a nidus for infection (i.e., cut or insect bite) along with surrounding erythema and pain. Necrotizing fasciitis may have overlying bullae along with systemic signs of infection such as fever, leukocytosis, elevated sedimentation rate and C-reactive protein with hyponatremia. Necrotizing fasciitis requires prompt diagnosis and early surgical debridement to prevent mortality and limb loss. Superficial thrombophlebitis involves an inflamed superficial vein in the upper extremity. This often resolves with limb elevation, warm compresses, and non-steroidal anti-inflammatory agents. Suppurative or septic superficial thrombophlebitis is associated with significant morbidity and mortality requiring prompt and aggressive intervention that includes excision of the infected vein. This occurs more commonly in patients with significant burns or intravenous drug abuse. Lymphedema can present with limb swelling but most commonly in the upper extremity occurs after a procedure such as axillary lymph node dissection.
The prognosis differs between primary and secondary forms. Patients with the primary form (PSS) of upper extremity DVT are typically young and healthy, while those with secondary forms are often previously hospitalized and may have significant co-morbidities such as cancer. In a large database study, overall 3-month mortality in patients with DVT in the upper extremity was 11%. In a sub-group analysis of patients with cancer, the mortality rate was as high as 28%. Complications such as PE and post-thrombotic syndrome can also occur. PE occurs in up to 6% of cases and occurs most often in secondary forms of upper extremity DVT. Post-thrombotic syndrome occurs in less than 5% of upper extremity DVT and can result in persistent limb swelling, pain, and heaviness. However, in patients with PSS, the post-thrombotic syndrome can occur in as high as 45% of cases. If this continues untreated, it can result in skin discoloration and collateralization. Investigations are underway to determine if compression therapy may help prevent and/or treat the post-thrombotic syndrome.
There continues to be controversy regarding prophylactic anticoagulation therapy in cancer patients with central venous catheterization. Several randomized controlled trials have not shown benefit in this patient population receiving warfarin or low molecular weight heparin.