European Journal of Cardiovascular Medicine

Paget-Von Schroetter syndrome (PVSS), first described by Sir James Paget in 1875 and subsequently characterized by Von Schroetter in 1884, represents a subset of upper extremity deep vein thrombosis (UEDVT). PVSS typically occurs in young, healthy individuals engaged in vigorous physical activities. This condition arises from the compression and recurrent injury of the subclavian vein where it passes through the first rib area, making it a recognized variant of thoracic outlet syndrome (TOS) [1]. The pathogenesis involves a combination of mechanical compression of the subclavian vein, endothelial injury and hypercoagulability, culminating in thrombus formation.

Early recognition and prompt initiation of anticoagulation therapy are essential to mitigate the risk of life threatening complications such as pulmonary embolism and improve patient outcomes.Differentiating catheter associated subclavian thrombosis and Paget-Von Schroetter syndrome is important because they appear to have different natural histories.

Current management strategies for effort thrombosis show considerable variation. Traditionally, conservative approaches involving anticoagulation and elevation of the affected arm were commonly employed but often failed to achieve symptom-free arm function, leading to dissatisfaction among many patients [2]. Persistent and recurrent thrombosis in post-thrombotic syndrome (PTS) is a significant concern following an initial episode of PVSS [3]. Recent consensus leans towards early adoption of catheter-directed thrombolytic therapy, which has demonstrated superior outcomes. Nevertheless, there remains a notable risk of recurrent thrombosis despite thrombolysis and anticoagulation alone. Balloon angioplasty has proven ineffective for long-term treatment of residual subclavian vein narrowing, and stent placement is generally discouraged. Therefore, surgical decompression of the thoracic outlet is favoured in recent times. However, consensus has yet to emerge regarding optimal patient selection, timing of intervention, or specific surgical techniques.

A 28-year-old male software engineer, presented to the emergency department with acute onset left arm swelling and pain after lifting heavy weights at the gym. He described progressive discomfort in the left shoulder and arm over several hours, exacerbated by movement. There was no history of trauma or recent illness. On examination,marked swelling and tenderness were noted over the right upper arm region. Duplex ultrasonography confirmed acute thrombosis of the left subclavian and axillary veins. The coagulation profile of the patient was normal. He was managed conservatively on Tab. Dabigatran 110mg, for 6 months. He was advised to avoid weight lifting and use compression bandage along with limb elevation. He responded well to the conservative management.

Pathophysiology:

It is sometimes referred to as a spontaneous axillary and subclavian vein thrombosis to express the usually dramatic unexpected presentation of the disorder in otherwise healthy, generally young individuals.

The pathophysiology of PVSS is multifactorial. It involves compressive changes of the vessel wall, stasis of blood and hypercoagulability. Compression of the axillary and subclavian vein leads to stasis of blood that results in thrombosis [4].

The factors that cause external compression include:

1. Abnormal subclavius or anterior scalene muscle, long transverse process of cervical spine, cervical rib, abnormal insertion of the first rib, congenital fibromuscular bands, or narrowing of costoclavicular space from depression of the shoulder
2. Stress from exercise temporarily causing hypercoagulability
3. Repetitive shoulder arm motion causing microscopic intimal tears in the vessel wall.

When these factors come together, they satisfy the classic Virchow’s triad for thrombosis. Furthermore, coexisting hematological abnormalities that can contribute to thrombosis include protein C deficiency, antithrombin III deficiency, factor V Leiden mutation and prothrombin 20210A mutation. Majority of the cases usually occur in the dominant upper extremity [5].

Differential Diagnosis

• Superficial phlebitis
• Cellulitis
• Lymphedema
• Muscular tear or Intramuscular hemorrhage
• Occult fracture
• Superior vena caval obstruction
• Localized allergic reaction

Diagnostic Approach

Diagnostic evaluation begins with a thorough clinical history and physical examination, focusing on identifying precipitating activities and anatomical abnormalities suggestive of thoracic outlet syndrome (TOS). Duplex ultrasonography is the initial imaging modality of choice due to its high sensitivity and specificity for detecting upper extremity deep vein thrombosis (UEDVT). Contrast venography is considered as a gold standard for diagnosis [4]. Computed tomography (CT) angiography and Magnetic resonance (MR) angiography is indicated to assess for underlying structural abnormalities contributing to thrombosis, such as cervical ribs or costoclavicular compression [6].

Management Strategies

The cornerstone of PVSS management is early initiation of anticoagulation therapy to prevent thrombus propagation and reduce the risk of pulmonary embolism. Initial therapy involves parenteral anticoagulation with low molecular weight heparin (LMWH), followed by transition to oral anticoagulants such as warfarin to achieve and maintain a therapeutic international normalized ratio (INR) of 2.0 to 3.0. There is shift towards newer anticoagulants, Dabigatran and Rivaroxaban as these are safer due to decreased risk of bleeding [5]. Analgesics, such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), are prescribed for pain relief. Temporary cessation of strenuous activities involving the affected limb is recommended to prevent exacerbation of symptoms and promote healing.

In cases where there is a high clinical suspicion of extensive thrombus burden or failure of conservative management, catheter-directed thrombolysis may be considered to dissolve thrombus and restore venous patency while minimizing the risk of post-thrombotic syndrome [7].

Surgical management of Paget-Schroetter syndrome is guided by specific criteria. Patients with symptomatic venous thoracic outlet syndrome (TOS) or recent effort thrombosis are eligible for surgical intervention, irrespective of prior treatments or findings on contrast venography [8]. Most common approach used involves para-clavicular thoracic outlet decompression. This technique combines supraclavicular and medial infraclavicular incisions, encompassing complete anterior and middle scalenectomy, brachial plexus neurolysis, subclavius muscle tendon excision, and resection of the entire first rib. Circumferential external venolysis is universally conducted, often resulting in the re-expansion of the subclavian vein to a normal diameter without further reconstruction in the majority of cases [1].

In instances where residual vein narrowing persists despite external venolysis, direct subclavian vein reconstruction can be performed using autologous saphenous vein or vein patch angioplasty. Some patients require subclavian vein bypass grafts, particularly those with obstructed segments. Postoperatively, therapeutic anticoagulation is initiated promptly, followed by transition to oral anticoagulants.

Secondary procedures are necessary for a subset of patients, primarily for complications like subclavian vein graft thrombosis. In these cases, interventions included thrombectomy, balloon angioplasty, or revision of the bypass graft.

Rehabilitation has to begin promptly after surgery to maintain upper extremity function, supervised by specialized physical therapists. 

Paget-Von Schroetter syndrome typically manifests acutely following activities involving repetitive or strenuous use of the upper limb, such as weightlifting, swimming, or sports activities like tennis or baseball. The syndrome's pathophysiology involves mechanical compression of the subclavian vein against the first rib or clavicle, leading to endothelial injury and subsequent thrombosis. Contributing factors include anatomical anomalies like cervical ribs or muscular abnormalities, which further predispose individuals to thrombus formation. Hypercoagulable states, such as genetic mutations (e.g., Factor V Leiden, prothrombin gene mutation) or acquired conditions (e.g., oral contraceptive use), may exacerbate thrombotic risk.

Paget-Von Schroetter syndrome is a rare but clinically significant cause of upper extremity deep vein thrombosis, particularly in young, physically active individuals. Early recognition, prompt initiation of anticoagulation, and comprehensive management strategies are crucial to prevent complications such as pulmonary embolism and chronic venous insufficiency. Continued research is necessary to refine diagnostic algorithms, optimize treatment modalities, and improve long-term outcomes for patients with PVSS.

1. de SiqueiraFilho, J. T., de Paula, R. L., Régis, A. C. A., Figueiredo, A. R., von Mühlen, B., & Peres, J. V. F. (2021). Paget-von Schroetter syndrome: Case report. International Journal of Surgery Case Reports, 88, 106509.
2. Spiezia, L., &Simioni, P. (2010). Upper extremity deep vein thrombosis. Internal and emergency medicine, 5, 103-109.
3. Prandoni, P., Bernardi, E., Marchiori, A., Lensing, A. W., Prins, M. H., Villalta, S., ...&Girolami, A. (2004). The long term clinical course of acute deep vein thrombosis of the arm: prospective cohort study. Bmj, 329(7464), 484-485.
4. de SiqueiraFilho, J. T., de Paula, R. L., Régis, A. C. A., Figueiredo, A. R., von Mühlen, B., & Peres, J. V. F. (2021). Paget-von Schroetter syndrome: Case report. International Journal of Surgery Case Reports, 88, 106509.
5. Ilhan, E., Ture, M., Yilmaz, C., &Arslan, M. (2009). Subclavian vein thrombosis extending into the internal jugular vein: Paget-von Schroetter Syndrome. Journal of Clinical Medicine Research, 1(3), 178.
6. Pejkova, S., Aleksovski, D., Hadjitrifon, S., Tusheva, S., Georgieva, G., Srbov, B., &Aszmann, O. C. (2023). Paget-Schroetter syndrome: the importance of early detection and effective surgical intervention. Archive of Clinical Cases, 10(4), 200.
7. Ibrahim, R., Dashkova, I., Williams, M., Kozikowski, A., Abrol, N., Gandhi, A., &Pekmezaris, R. (2017). Paget-Schroetter syndrome in the absence of common predisposing factors: a case report. Thrombosis journal, 15, 1-4.
8. Roche-Nagle, G., Ryan, R., Barry, M., &Brophy, D. (2007). Effort thrombosis of the upper extremity in a young sportsman: Paget–Schroetter syndrome. British journal of sports medicine, 41(8), 540-541.