Paget-Schroetter Syndrome
- Incidence: 1-2/100,000 individuals/year
About 3,000-6,000 cases per year in the U.S. - FDA-approved treatments: Anticoagulation including
heparin and oral anticoagulants - Social media hashtags: #thoracicoutletsyndrome,
#RareDiseaseDay - Resources: rarediseases.org/rare-diseases/thoracic-outlet-syndrome/
mayoclinic.org/diseases-conditions/
thoracic-outlet-syndrome/symptoms-causes/syc-20353988
Paget-Schroetter syndrome, also known as venous thoracic outlet syndrome or primary effort thrombosis, was first described in 1949 by Edward Hughes, a British surgeon who saw patients with spontaneous or stress thrombosis of the subclavian or axillary vein, deep veins, and among the major veins that drain the upper extremities in the body. Dr. Hughes named the syndrome “Paget-Schroetter” after two clinicians: Sir James Paget, who reported a case of spontaneous thrombosis of the subclavian vein in a patient in 1875, and Leopold von Schröetter, an Austrian internist and laryngologist who hypothesized in 1884 that this clotting condition was a consequence of injury to the vein from repetitive musculoskeletal motion.
“Paget-Schroetter syndrome is one of three thoracic outlet syndromes that occur when blood vessels or nerves are compressed between the collarbone and the first rib within the thoracic outlet,” explained Marc S. Zumberg, MD, a hematologist at University of Florida Health in Gainesville. “It is much less common than compression of the nerve (95% of cases), but more common than compression of the accompanying artery, which is about 1% of cases.”
ASH Clinical News spoke with Dr. Zumberg and Alejandro Lazo-Langner, MD, the chief of the division of hematology at the London Health Sciences Centre in Ontario, Canada, about diagnosing and managing this rare disorder.
Development and Presentation
“The cause, we believe, is a compressed anatomical area surrounding the vein combined with repeated upward motions of the arm over time that causes the vein compression and injury,” Dr. Zumberg said.
Repeated compressions of the subclavian vein over time can damage the lining, and thrombosis of the vein can eventually occur. The compression of the subclavian vein can be a result of hypertrophy of the surrounding muscle from a recurring movement, which decreases the space for the vein.1
Another indication that Pagett-Schroetter syndrome may be present is if a younger patient in their 20s or 30s presents with a blood clot in their arm but doesn’t have underlying risk factors for clotting. In this case, Dr. Zumberg said he would strongly consider Pagett-Schroetter syndrome.
In terms of anatomical risk factors, an abnormal cervical rib, which occurs in under 6% of the population,2 can also contribute to pinching of one of the veins in the thoracic outlet. Another possible cause of vein compression is a more lateral insertion of the costoclavicular ligament. Any or all of these anatomic abnormalities can lead to an increased risk of vein compression, repeated damage, and finally blood clotting in the subclavian vein.
Individuals who form blood clots may have an underlying disorder that makes them more prone to clotting through the body. Blood clots can also arise from cancer when a tumor or abnormal growth pushes on a vein. Blood clots in the arm can also occur as a result of frequent catheter placement.
However, “Paget-Schroetter syndrome is typically due to mechanical reasons rather than a true, underlying hematologic disorder,” Dr. Zumberg said. “Young, otherwise healthy individuals – including athletes such as weightlifters, baseball players, and swimmers, or workers in occupations that require the same repeated overhead motion such as mechanics, electricians, and painters – are the typical individuals that are diagnosed with Paget-Schroetter syndrome.”
The blood clot tends to form in the patient’s dominant arm because of its more frequent use, and following recurring, raised-position movements that cause the vein to become pinched over time.
The syndrome is more common in men than in women, by a ratio of two to one, and more frequently occurs on the right side, due to the higher prevalence of right-hand dominance. The estimated incidence is around one to two individuals per 100,000 per year. Compared to the one to two patients per thousand per year who are diagnosed with a deep vein thrombosis (DVT) in the leg, the syndrome is quite rare.3
Diagnosis
The most common initial symptoms are acute pain and swelling near the shoulder or in the chest. Patients can also present with congestion of the veins around the chest and shoulder area, or they might even have engorged veins in the chest.
“These patients usually go to an emergency facility as a result of the symptoms and need to be assessed for thrombosis,” Dr. Lazo-Langner said.
“Once there is a clinical suspicion of a potential blood clot, we do imaging, usually ultrasonography, of the upper extremities to check for thrombus in the deep venous system,” he added.
In some cases, computed tomography (CT), venography, or magnetic venography is needed to image the central veins and identify or rule out thrombus since a non-vascular CT scan is sometimes not enough to view all of the veins – for example, in patients who are larger or those with a thoracic deformity venography.
“The vast majority of patients we see with upper extremity clots have clots that are related to catheters for chemotherapy or antibiotics or due to a tumor,” Dr. Lazo-Langner said. “Primary upper extremity [DVT] due to this syndrome is a very small minority of patients.”
In a commentary published in Research and Practice in Thrombosis and Haemostasis, Dr. Lazo-Langner noted that upper extremity DVT itself is a relatively uncommon form of venous thrombosis.4 It accounts for 5% to 10% of all DVTs, with an annual incidence of 0.5 to 1 case per 10,000 patient-years.
Thrombophilia testing, including protein C and S levels, antithrombin levels, prothrombin gene mutation analysis, and factor V Leiden, are not typically needed unless there is other personal or a strong family history of thrombosis. If the patient has symptoms related to a pulmonary embolism (PE), a CT pulmonary angiography with a PE protocol should be conducted.
“The diagnosis is often missed, I think, because this disorder is so rare,” Dr. Zumberg said. “When a clot is found, the patient is typically put on anticoagulant treatment, but the clinician may not suspect this syndrome, and the patient is left at risk for recurrent thrombosis.”
It’s important to note that this syndrome can occur in otherwise healthy patients, he added. To help with diagnosis, vein imaging should be taken both with the patient’s arms down and with them raised because it’s easier to see the vein compression or pinching when the arms are raised.
“The risk of recurrence [of a DVT] is about 3.5% overall, but for Paget-Schroetter syndrome, the rate is likely higher,” Dr. Lazo-Langner said.
Two-Part Treatment
The initial treatment for diagnosed patients is anticoagulation therapy, either low-molecular-weight heparin or an oral anticoagulant such as rivaroxaban or apixaban. Patients are kept on maintenance anticoagulation therapy for three to six months following the DVT episode. Six months of therapy is reasonable, according to a study published by Dr. Lazo-Langner and co-authors in 2015,5 but there are no studies that compare treatment duration with outcomes to define exactly how long patients need to stay on anticoagulation therapy.
Treatment may also include a form of catheter-directed thrombolysis to encourage venous drainage and relieve pressure, especially if the patient is in pain, Dr. Lazo-Langner added. He also recommended that patients consult with a vascular surgeon to see whether decompression surgery is an option. If so, anticoagulation therapy can be discontinued after the surgery.
Treatment approaches differ between the U.S. and Canada, according to Dr. Lazo-Langner. In Canada, for example, thrombolysis is not recommended because there is no robust evidence suggesting that the procedure improves outcomes, and it is associated with a higher risk of bleeding that is not negligible.
Decompression of the thoracic outlet is thought to be the major management of the syndrome. Decompression typically includes a first rib resection with one or all of the following procedures: resection of the subclavius muscle, an anterior scalenectomy, resection of the costoclavicular ligament, and lysis of scar tissue and adhesions surrounding the subclavian vein.
“If the muscles are really hypertrophied, a partial resection of the muscle might be necessary, but after the anatomical issue is dealt with, and after recovery from surgery, patients can go back to their normal activities. The outcome is usually quite good,” Dr. Zumberg said.
The success rate for a full recovery within about a year is around 90-95%.3
A 2021 meta-analysis of 25 studies discussed therapeutic outcomes for Paget-Schroetter syndrome.6 Out of 1,511 patients, 77.9% underwent thrombolysis (n=1,177), 85.6% underwent decompression therapy of the thoracic outlet (n=1,293), and 43.5% received anticoagulation therapy (n=658). Because it was a meta-analysis, there were no clear statistics on the number of patients that received any of the combination of therapies. Of the patients that underwent thrombolysis, complete thrombus resolution was estimated to be 78%, and 11.2% had no resolution of thrombus following thrombolysis.6 After anticoagulation therapy, 40.7% had complete thrombus resolution, partial resolution occurred in 29.1% of patients, and 30.2% had no resolution. During follow-up, 84.8% of patients were free of symptoms.
Both Drs. Zumberg and Lazo-Langner would like to see randomized studies comparing outcomes with different interventions including anticoagulants, thrombolysis, and decompression therapy of the thoracic outlet.
References
- Saleem T, Baril DT. Paget-Schroetter StatPearls. Updated January 11, 2022. https://www.ncbi.nlm.nih.gov/books/NBK482416/#article-36509.s3.
- Spadliński L, Cecot T, Majos A, et al. The epidemiological, morphological, and clinical aspects of the cervical ribs in humans. Biomed Res Int. 2016; 2016:8034613.
- Illig KA, Doyle AJ. A comprehensive review of Paget-Schroetter. J Vasc Surg. 2020;51(6):1538-1547.
- Lazo-Langner A. Studies in upper extremity deep vein thrombosis: addressing the knowledge gaps. Res Pract Thromb Haemost. 2019;3(3):312-314.
- Lazo-Langner A, Kahn SR, Wells PS, et al. A prospective cohort study of upper extremity deep vein thrombosis. Blood. 2015;126(23):893.
- Karaolanis G, Antonopoulos CN, Koutsias SG, et al. A systematic review and meta-analysis for the management of Paget-Schroetter syndrome. J Vasc Surg. 2021;9(3):801-810.e5.