Introduction
Deep vein thrombosis (DVT) of the upper extremities comprises approximately 10% of all deep vein thromboses, with an incidence of 4 to 10 patients per 100 000 population (1). There are two types – primary DVT induced by effort, i.e., Paget-Schroetter syndrome, comprising approximately 20% of all DVTs of the upper extremities, and the much more common secondary DVT, which is associated with the application of central venous catheters and therapy or dialysis (tunneled or non-tunneled) cardiac pacemaker leads and ports (1,2).
Paget-Schroetter syndrome (PSS) is thrombosis of the subclavian vein induced by exertion, often concomitant with thrombosis of the axillary and cephalic vein. It was described near the end of the 19th century by two authors (Sir James Paget and Leopold von Schroetter), who observed effort-induced subclavian vein thrombosis mostly in young, otherwise healthy men (3). It represents a subtype of the venous type of thoracic outlet syndrome (TOS) (4). TOS refers to a spectrum of states that occur due to compression injury or irritation to structures passing through the superior thoracic aperture, the space in the lower part of the neck / upper part of thorax, between the collarbone and the first rib, containing the brachial plexus and the subclavian vein and artery. The costoclavicular ligament is located medially from the subclavian vein, and the anterior scalene muscle is located laterally. The most common type of TOS is neurogenic, developing due to compression of the brachial plexus and manifesting as pain and weakness in the affected arm (2,4,5).
Venous TOS has three subtypes: primary DVT (PSS), secondary DVT, and positional venous obstruction (4,5).
PSS is a rare condition, with an incidence of 1 to 2 per 100 000 population, is twice as common in men as in women, and is more common on the right side. It is associated with repetitive movements of the affected shoulder (a consequence of work in some professions, or in professional or amateur athletes). Arm abduction leads to compression of the subclavian vein between the clavicle and the first rib, which is the basis for Virchow’s triad (2). Other anatomic factors that contribute to the development of thrombosis include abnormal formation of the first rib, congenital bands, or the presence of a cervical rib, and can be additionally influenced by concomitant hematological states (2).
Clinical manifestations of PSS are venous distension, swelling in the affected arm, bluish discoloration, and pain (sometimes with pain exacerbation after exercise). In addition to anamnesis, the clinical picture, and d-dimers (which do not have great clinical significance), the method of choice for imaging is Color Doppler ultrasound. Other diagnostic methods include venography as well as CT and MR of the neck and the superior thoracic aperture (1,2,4-6).
Treatment strategies for PSS include anticoagulation treatment lasting a minimum of three months (low-molecular-weight heparin, new oral anticoagulants, vitamin K antagonists), thrombi removal (catheter-directed thrombolysis or pharmacomechanic thrombolysis), and surgical treatment – decompression of the thoracic aperture by resection of the first rib.
Case report
A 37-year-old amateur body-builder and boxer, previously healthy, a non-smoker, with negative family history for cardiovascular diseases, who was not receiving any chronic treatment but was taking testosterone supplements (once per week applied intramuscularly), presented at the Joint Hospital Admission of the Rijeka Clinical Hospital Center due to swelling of the left arm (Figure 1,Figure 2). The symptoms had been present for four days before admission. Ultrasound examination found DVT of the left subclavian, axillary, and cephalic veins. Laboratory findings showed mild neutrophilic leukocytosis with only mildly elevated C-reactive protein levels (L 10.3 x 109/L, neutrophiles 76.3%, CRP 11 mg/L). The chest radiograph was normal, and 12-lead electrocardiogram examination verified sinus rhythm with a ventricular frequency of 90/min and inferolaterally flattened T-waves. Treatment was initiated at the Department for Vascular Surgery using a therapy dose of low-molecular-weight heparin, which was continued for nine days. Despite the treatment, no clinical improvement was observed. On the ninth day of hospitalization, the patient’s case was presented at the vascular surgeon and cardiologist consilium, and percutaneous aspiration thrombectomy was indicated.
After appropriately preparing the patient, the femoral vein approach was used to place a 6 French (F) sheath and a multipurpose angiographic (MPA) catheter at the origin of the left subclavian vein. A Gaia 3rd guide wire was used to bypass the proximal cap of the occlusion, and the application of a NC 4.5 x 15 mm balloon catheter was used to successfully proceed to the projection of the origin of the cephalic vein, but the guidewire was unable to continue towards the axillary vein. Subsequently, ultrasound control was used to place a 6 F sheath into the cubital vein, and a hydrophilic guide wire as used to bypass the occlusion point, now using an anterograde approach, and the guide wire was placed distally in the inferior vena cava. A rheolytic thrombectomy was performed using an Angiojet Omni catheter. Two 8 x 40 mm and 12 x 40 mm balloon catheters were used to dilate the entire occluded segment. The final venogram indicated restored flow in the axillary and subclavian vein, with still visible subclavicular thrombotic masses (Figures 3-7{ label needed for fig[@id='f4'] }{ label needed for fig[@id='f5'] }{ label needed for fig[@id='f6'] }{ label needed for fig[@id='f7'] }).
Regression of symptoms and clinical improvement (visible regression of the arm swelling and increased mobility) were observed on the second day after the intervention. Venography was performed (through the right cubital vein due to the still pronounced swelling of the left arm), which verified normal dimensions of the veins of the left arm, with partial thrombotic obstruction. Venous ultrasound of the arm was performed on the second day after the intervention, 14 days after the intervention, and four months after that. It found a residual thrombus in the subclavian vein, but with partial flow around the thrombus (Figure 8).
A thoracic surgeon was consulted regarding decompression treatment, who stated that surgical treatment was not indicated, but that anticoagulation treatment should be continued, along with magnetic resonance imaging of the neck and superior thoracic aperture. Imaging showed stenosis of the left subclavian vein in the area of the left costoclavicular space, with two tiny residual thrombi with a longer diameter of 6 mm. It was also clearly shown that the lower wall of the left subclavian vein was touching the upper edge of the left first rib (Figures 9-12{ label needed for fig[@id='f10'] }{ label needed for fig[@id='f11'] }{ label needed for fig[@id='f12'] }).
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The patient was discharged on the fourth day after the intervention, with peroral rivaroxaban anticoagulation therapy. Molecular analysis of thrombophilic factors showed a normal gene type for factor V Leiden and prothrombin (II). The value of antithrombin III was normal, as was protein S, and lupus anticoagulant was not found, whereas the value of protein C was mildly lowered (0.61).
On follow-up, the patient reported subjective improvement, regularly taking the recommend therapy, and reducing exercise intensity for the left arm. Clinical status was dominated by the development of superficial venous collaterals on the left side of the chest (i.e., Urschel’s sign) (Figure 13). The patient stated that he still observed a bluish tinge on the skin of the arm and mild swelling after longer exercise sessions. The patient’s case will be reviewed for treatment for PSS – decompression of the upper thoracic aperture by resection of the first rib.
Discussion
Although PSS is relatively rare in the general population, the disease is an important clinical entity which must be occasionally recognized and treated adequately. It presents in the younger, professionally active population and is thus often overlooked or diagnosed late, which increases the likelihood of complications and permanent damage. In a certain percentage of cases (7-20%), DVT of the upper extremities is concomitant with pulmonary thromboembolism (5). According to current guidelines, treatment strategy that includes thrombus removal is only viable during the first two weeks from symptom onset, since thrombus organization takes place after that period, along with the development of collaterals (1). Secondly, PSS should be differentiated from secondary deep vein thrombosis of the upper extremities, always bearing in mind that idiopathic thromboses can be the first sign of malignant disease. Furthermore, the patient described herein was taking testosterone supplements, the (ab)use of which is a growing issue. A number of studies have clearly demonstrated the association between their application and the incidence of deep vein thrombosis (7).
The next question at issue is the duration of the application of anticoagulation therapy. Minimal therapy lasts for three months. It is important to carefully consider the likelihood of recidivism as well as the concomitant states and diseases, and consequently decide on the best treatment modality and duration of anticoagulation therapy.
In our patient, we also performed tests for hereditary thrombophilia, but routine screening for it is not recommended on the first manifestation of DVT (with or without the presence of provoking factors) (1).
Although most patients experience regression of symptoms after treatment with anticoagulation therapy, the present patient demanded interventional treatment. Systemic thrombolysis is not recommended due to possible complications, but there are various treatment modalities for interventional treatment (catheter-directed thrombolysis, pharmacomechanic thrombolysis), including percutaneous aspiration thrombectomy, as applied in the present case.
The ultimate treatment for PSS is surgery – decompression by resection of the first rib (with several possible approaches; transaxillary, supraclavian, intraclavian) (8). Treatment choice should consider the fact that surgical treatment is not free of possible complications (hemopneumothorax, structural damage in the thoracic area and elsewhere).
In conclusion, PSS is a complex syndrome that requires early diagnosis and a multidisciplinary approach, with a variety of available treatment options.