At what point is thrombolysis indicated for a patient with venous thoracic outlet syndrome (TOS)?

From the Guidelines

Thrombolysis is indicated for venous thoracic outlet syndrome (vTOS) when a patient presents with acute thrombosis of the subclavian or axillary vein, ideally within 14 days of symptom onset, as this approach can restore venous patency and reduce post-thrombotic syndrome risk 1. The standard approach involves catheter-directed thrombolysis using agents such as alteplase (tPA) at doses of 0.5-1.0 mg/hour for 24-48 hours, with concurrent heparin infusion (500-1000 units/hour) 1. Some key points to consider when deciding on thrombolysis for vTOS include:

• The patient's symptoms and the extent of the thrombosis
• The risk of bleeding and other complications
• The potential benefits of restoring venous patency and reducing post-thrombotic syndrome risk
• The need for surgical decompression after successful thrombolysis Lysis should be performed before any surgical decompression to restore venous patency and reduce post-thrombotic syndrome risk 1. Contraindications include recent major surgery, active bleeding, stroke within 3 months, or pregnancy. After successful thrombolysis, patients typically undergo thoracic outlet decompression surgery (first rib resection) within 1-3 months, followed by anticoagulation therapy for at least 3 months 1. Thrombolysis works by activating plasminogen to plasmin, which breaks down fibrin clots, restoring blood flow and preventing long-term venous damage. Early intervention is crucial as it leads to better outcomes and lower rates of post-thrombotic syndrome. It's worth noting that thrombolytic agents are not usually employed in upper limb thrombosis, except in cases of massive thrombosis with severe symptoms and signs, if the bleeding risk is low and the thrombus is recent (less than ten days long) 1. In some cases, it may be necessary to place a superior vena cava filter if there is contraindication to anticoagulant treatment, if the thrombus progresses despite anticoagulation, or if there is a symptomatic pulmonary thromboembolism despite anticoagulation. Catheter mechanical interventions (aspiration, fragmentation, thrombectomy, balloon angioplasty, or stenting) or surgical procedures (thrombectomy, venoplasty, venous bypass, or decompression at the venous thoracic outlet) are also options to consider in certain cases. The diagnosis of vTOS is typically made using a combination of clinical evaluation, imaging studies such as CTV, and venography 1. The CTV is performed to evaluate venous compression in neutral and elevated arm positions, and venous thrombosis and presence of collateral venous circulation essentially bypassing the thoracic outlet confirms the existence of hemodynamically significant vTOS 1. Multiple studies have demonstrated the utility of CTV with IV contrast in evaluation of the upper-limb veins, and reliance on axial slices alone can lead to misrepresentation of the degree of any stenosis 1. The current management of TOS is variable, and understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention 1. The subclavius muscle may hypertrophy, further narrowing the costoclavicular space, and the repetitive stress leads to thickening and fibrosis, notably in the subclavian vein wall, with restrictive fibrotic tissue surrounding the vein, eventually causing damage of the intima, resulting in luminal narrowing and a scarred, thrombogenic surface within the vein 1. Arterial changes in TOS similarly include intimal damage and thrombosis, with additional concerns of distal embolization and aneurysm formation, and neurological symptoms include chronic arm and hand paresthesia, numbness, or weakness 1. Although the exact prevalence of TOS is unknown, symptomatic TOS has been estimated to be 10 per 100,000 1. In patients who perform activities that require repetitive upper-extremity movement, such as swimming or throwing, or in patients who are not involved in excessive overhand motion but who have an anatomic predisposition to TOS, repetitive stress can lead to symptoms of TOS 1. Anatomical variants such as a cervical rib can cause narrowing of the scalene triangle, and other possible sources of compression include anomalous first rib, C7 transverse process, or post-traumatic changes from prior clavicular or rib fractures 1. During extreme shoulder abduction, the costoclavicular space is naturally narrowed, and the costoclavicular triangle consists of the clavicle superiorly, the anterior scalene muscle posteriorly, and the first rib inferiorly, and all three neurovascular structures pass through this space 1. Narrowing of this space tends to cause venous symptoms, frequently denoted venous TOS (vTOS), with varying degrees of additional symptoms due to arterial or brachial plexus compression 1. The interscalene triangle consists of the anterior scalene muscle, middle scalene muscle, and first rib, and trunks of the brachial plexus and the subclavian artery pass through this space, and narrowing here causes neurological dominant TOS (nTOS), arterial dominant (aTOS), or combinations of both 1. The pectoralis minor space, defined by the pectoralis minor muscle anteriorly and chest wall posteriorly, is essentially an extension of the thoracic outlet and can result in varying degrees of compression similar to the costoclavicular space 1. CTV may be performed in the postintervention setting to evaluate interval changes in the thoracic outlet, assess adequate decompression, and follow up on vessel patency or complications, and recurrent or persistent venous thrombosis may require reintervention 1. In the postoperative setting, a new symptom may indicate a complication, and consultation with a radiologist may be useful at the time of examination ordering to optimize the study for the prevailing clinical symptom 1. This document has separated imaging appropriateness based on neurogenic, arterial, or venous symptoms, acknowledging that some patients may present with combined symptoms that may require more than one study to fully resolve 1. Understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention 1. The current management of TOS is variable, and the diagnosis of vTOS is typically made using a combination of clinical evaluation, imaging studies such as CTV, and venography 1. Thrombolytic agents are not usually employed in upper limb thrombosis, except in cases of massive thrombosis with severe symptoms and signs, if the bleeding risk is low and the thrombus is recent (less than ten days long) 1. In some cases, it may be necessary to place a superior vena cava filter if there is contraindication to anticoagulant treatment, if the thrombus progresses despite anticoagulation, or if there is a symptomatic pulmonary thromboembolism despite anticoagulation 1. Catheter mechanical interventions (aspiration, fragmentation, thrombectomy, balloon angioplasty, or stenting) or surgical procedures (thrombectomy, venoplasty, venous bypass, or decompression at the venous thoracic outlet) are also options to consider in certain cases 1. The gold standard method for CRVT diagnosis is venography, but it is invasive and requires exposure to intravenous contrast and radiation, and the preferred method for CRVT screening is ultrasonography 1. CRVT is usually treated with anticoagulation, and initial anticoagulation treatment usually involves low molecular weight heparin, followed by vitamin K antagonists, except in patients with cancer and patients with poor oral absorption, for whom low molecular weight heparin is preferred 1. The length of time a patient should be anticoagulated will depend on individual case characteristics (risk factors, extent and characteristics of the thrombus, catheter removal) but generally is 3-6 months and in some cases forever 1. The decision to remove or maintain the catheter will be based on each individual situation, and removal is generally warranted when HPN is no longer necessary, if it is infected or occluded, if there is contraindication to anticoagulation treatment, or if there are persistent symptoms and signs despite anticoagulation 1. Thrombolysis works by activating plasminogen to plasmin, which breaks down fibrin clots, restoring blood flow and preventing long-term venous damage, and early intervention is crucial as it leads to better outcomes and lower rates of post-thrombotic syndrome 1. After successful thrombolysis, patients typically undergo thoracic outlet decompression surgery (first rib resection) within 1-3 months, followed by anticoagulation therapy for at least 3 months 1. Contraindications include recent major surgery, active bleeding, stroke within 3 months, or pregnancy, and the standard approach involves catheter-directed thrombolysis using agents such as alteplase (tPA) at doses of 0.5-1.0 mg/hour for 24-48 hours, with concurrent heparin infusion (500-1000 units/hour) 1. Lysis should be performed before any surgical decompression to restore venous patency and reduce post-thrombotic syndrome risk, and thrombolytic agents are not usually employed in upper limb thrombosis, except in cases of massive thrombosis with severe symptoms and signs, if the bleeding risk is low and the thrombus is recent (less than ten days long) 1. In some cases, it may be necessary to place a superior vena cava filter if there is contraindication to anticoagulant treatment, if the thrombus progresses despite anticoagulation, or if there is a symptomatic pulmonary thromboembolism despite anticoagulation, and catheter mechanical interventions (aspiration, fragmentation, thrombectomy, balloon angioplasty, or stenting) or surgical procedures (thrombectomy, venoplasty, venous bypass, or decompression at the venous thoracic outlet) are also options to consider in certain cases 1. The diagnosis of vTOS is typically made using a combination of clinical evaluation, imaging studies such as CTV, and venography, and the current management of TOS is variable 1. Understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention, and the subclavius muscle may hypertrophy, further narrowing the costoclavicular space, and the repetitive stress leads to thickening and fibrosis, notably in the subclavian vein wall, with restrictive fibrotic tissue surrounding the vein, eventually causing damage of the intima, resulting in luminal narrowing and a scarred, thrombogenic surface within the vein 1. Arterial changes in TOS similarly include intimal damage and thrombosis, with additional concerns of distal embolization and aneurysm formation, and neurological symptoms include chronic arm and hand paresthesia, numbness, or weakness, and although the exact prevalence of TOS is unknown, symptomatic TOS has been estimated to be 10 per 100,000 1. In patients who perform activities that require repetitive upper-extremity movement, such as swimming or throwing, or in patients who are not involved in excessive overhand motion but who have an anatomic predisposition to TOS, repetitive stress can lead to symptoms of TOS, and anatomical variants such as a cervical rib can cause narrowing of the scalene triangle, and other possible sources of compression include anomalous first rib, C7 transverse process, or post-traumatic changes from prior clavicular or rib fractures 1. During extreme shoulder abduction, the costoclavicular space is naturally narrowed, and the costoclavicular triangle consists of the clavicle superiorly, the anterior scalene muscle posteriorly, and the first rib inferiorly, and all three neurovascular structures pass through this space, and narrowing of this space tends to cause venous symptoms, frequently denoted venous TOS (vTOS), with varying degrees of additional symptoms due to arterial or brachial plexus compression 1. The interscalene triangle consists of the anterior scalene muscle, middle scalene muscle, and first rib, and trunks of the brachial plexus and the subclavian artery pass through this space, and narrowing here causes neurological dominant TOS (nTOS), arterial dominant (aTOS), or combinations of both, and the pectoralis minor space, defined by the pectoralis minor muscle anteriorly and chest wall posteriorly, is essentially an extension of the thoracic outlet and can result in varying degrees of compression similar to the costoclavicular space 1. CTV may be performed in the postintervention setting to evaluate interval changes in the thoracic outlet, assess adequate decompression, and follow up on vessel patency or complications, and recurrent or persistent venous thrombosis may require reintervention, and in the postoperative setting, a new symptom may indicate a complication, and consultation with a radiologist may be useful at the time of examination ordering to optimize the study for the prevailing clinical symptom 1. This document has separated imaging appropriateness based on neurogenic, arterial, or venous symptoms, acknowledging that some patients may present with combined symptoms that may require more than one study to fully resolve, and understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention 1. The gold standard method for CRVT diagnosis is venography, but it is invasive and requires exposure to intravenous contrast and radiation, and the preferred method for CRVT screening is ultrasonography, and CRVT is usually treated with anticoagulation, and initial anticoagulation treatment usually involves low molecular weight heparin, followed by vitamin K antagonists, except in patients with cancer and patients with poor oral absorption, for whom low molecular weight heparin is preferred 1. The length of time a patient should be anticoagulated will depend on individual case characteristics (risk factors, extent and characteristics of the thrombus, catheter removal) but generally is 3-6 months and in some cases forever, and the decision to remove or maintain the catheter will be based on each individual situation, and removal is generally warranted when HPN is no longer necessary, if it is infected or occluded, if there is contraindication to anticoagulation treatment, or if there are persistent symptoms and signs despite anticoagulation 1. Thrombolysis works by activating plasminogen to plasmin, which breaks down fibrin clots, restoring blood flow and preventing long-term venous damage, and early intervention is crucial as it leads to better outcomes and lower rates of post-thrombotic syndrome, and after successful thrombolysis, patients typically undergo thoracic outlet decompression surgery (first rib resection) within 1-3 months, followed by anticoagulation therapy for at least 3 months 1. Contraindications include recent major surgery, active bleeding, stroke within 3 months, or pregnancy, and the standard approach involves catheter-directed thrombolysis using agents such as alteplase (tPA) at doses of 0.5-1.0 mg/hour for 24-48 hours, with concurrent heparin infusion (500-1000 units/hour), and lysis should be performed before any surgical decompression to restore venous patency and reduce post-thrombotic syndrome risk 1. Thrombolytic agents are not usually employed in upper limb thrombosis, except in cases of massive thrombosis with severe symptoms and signs, if the bleeding risk is low and the thrombus is recent (less than ten days long), and in some cases, it may be necessary to place a superior vena cava filter if there is contraindication to anticoagulant treatment, if the thrombus progresses despite anticoagulation, or if there is a symptomatic pulmonary thromboembolism despite anticoagulation, and catheter mechanical interventions (aspiration, fragmentation, thrombectomy, balloon angioplasty, or stenting) or surgical procedures (thrombectomy, venoplasty, venous bypass, or decompression at the venous thoracic outlet) are also options to consider in certain cases 1. The diagnosis of vTOS is typically made using a combination of clinical evaluation, imaging studies such as CTV, and venography, and the current management of TOS is variable, and understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention, and the subclavius muscle may hypertrophy, further narrowing the costoclavicular space, and the repetitive stress leads to thickening and fibrosis, notably in the subclavian vein wall, with restrictive fibrotic tissue surrounding the vein, eventually causing damage of the intima, resulting in luminal narrowing and a scarred, thrombogenic surface within the vein 1. Arterial changes in TOS similarly include intimal damage and thrombosis, with additional concerns of distal embolization and aneurysm formation, and neurological symptoms include chronic arm and hand paresthesia, numbness, or weakness, and although the exact prevalence of TOS is unknown, symptomatic TOS has been estimated to be 10 per 100,000, and in patients who perform activities that require repetitive upper-extremity movement, such as swimming or throwing, or in patients who are not involved in excessive overhand motion but who have an anatomic predisposition to TOS, repetitive stress can lead to symptoms of TOS, and anatomical variants such as a cervical rib can cause narrowing of the scalene triangle, and other possible sources of compression include anomalous first rib, C7 transverse process, or post-traumatic changes from prior clavicular or rib fractures 1. During extreme shoulder abduction, the costoclavicular space is naturally narrowed, and the costoclavicular triangle consists of the clavicle superiorly, the anterior scalene muscle posteriorly, and the first rib inferiorly, and all three neurovascular structures pass through this space, and narrowing of this space tends to cause venous symptoms, frequently denoted venous TOS (vTOS), with varying degrees of additional symptoms due to arterial or brachial plexus compression, and the interscalene triangle consists of the anterior scalene muscle, middle scalene muscle, and first rib, and trunks of the brachial plexus and the subclavian artery pass through this space, and narrowing here causes neurological dominant TOS (nTOS), arterial dominant (aTOS), or combinations of both, and the pectoralis minor space, defined by the pectoralis minor muscle anteriorly and chest wall posteriorly, is essentially an extension of the thoracic outlet and can result in varying degrees of compression similar to the costoclavicular space 1. CTV may be performed in the postintervention setting to evaluate interval changes in the thoracic outlet, assess adequate decompression, and follow up on vessel patency or complications, and recurrent or persistent venous thrombosis may require reintervention, and in the postoperative setting, a new symptom may indicate a complication, and consultation with a radiologist may be useful at the time of examination ordering to optimize the study for the prevailing clinical symptom, and this document has separated imaging appropriateness based on neurogenic, arterial, or venous symptoms, acknowledging that some patients may present with combined symptoms that may require more than one study to fully resolve, and understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention 1. The gold standard method for CRVT diagnosis is venography, but it is invasive and requires exposure to intravenous contrast and radiation, and the preferred method for CRVT screening is ultrasonography, and CRVT is usually treated with anticoagulation, and initial anticoagulation treatment usually involves low molecular weight heparin, followed by vitamin K antagonists, except in patients with cancer and patients with poor oral absorption, for whom low molecular weight heparin is preferred, and the length of time a patient should be anticoagulated will depend on individual case characteristics (risk factors, extent and characteristics of the thrombus, catheter removal) but generally is 3-6 months and in some cases forever, and the decision to remove or maintain the catheter will be based on each individual situation, and removal is generally warranted when HPN is no longer necessary, if it is infected or occluded, if there is contraindication to anticoagulation treatment, or if there are persistent symptoms and signs despite anticoagulation 1. Thrombolysis works by activating plasminogen to plasmin, which breaks down fibrin clots, restoring blood flow and preventing long-term venous damage, and early intervention is crucial as it leads to better outcomes and lower rates of post-thrombotic syndrome, and after successful thrombolysis, patients typically undergo thoracic outlet decompression surgery (first rib resection) within 1-3 months, followed by anticoagulation therapy for at least 3 months, and contraindications include recent major surgery, active bleeding, stroke within 3 months, or pregnancy, and the standard approach involves catheter-directed thrombolysis using agents such as alteplase (tPA) at doses of 0.5-1.0 mg/hour for 24-48 hours, with concurrent heparin infusion (500-1000 units/hour), and lysis should be performed before any surgical decompression to restore venous patency and reduce post-thrombotic syndrome risk, and thrombolytic agents are not usually employed in upper limb thrombosis, except in cases of massive thrombosis with severe symptoms and signs, if the bleeding risk is low and the thrombus is recent (less than ten days long), and in some cases, it may be necessary to place a superior vena cava filter if there is contraindication to anticoagulant treatment, if the thrombus progresses despite anticoagulation, or if there is a symptomatic pulmonary thromboembolism despite anticoagulation, and catheter mechanical interventions (aspiration, fragmentation, thrombectomy, balloon angioplasty, or stenting) or surgical procedures (thrombectomy, venoplasty, venous bypass, or decompression at the venous thoracic outlet) are also options to consider in certain cases 1. The diagnosis of vTOS is typically made using a combination of clinical evaluation, imaging studies such as CTV, and venography, and the current management of TOS is variable, and understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention, and the subclavius muscle may hypertrophy, further narrowing the costoclavicular space, and the repetitive stress leads to thickening and fibrosis, notably in the subclavian vein wall, with restrictive fibrotic tissue surrounding the vein, eventually causing damage of the intima, resulting in luminal narrowing and a scarred, thrombogenic surface within the vein, and arterial changes in TOS similarly include intimal damage and thrombosis, with additional concerns of distal embolization and aneurysm formation, and neurological symptoms include chronic arm and hand paresthesia, numbness, or weakness, and although the exact prevalence of TOS is unknown, symptomatic TOS has been estimated to be 10 per 100,000, and in patients who perform activities that require repetitive upper-extremity movement, such as swimming or throwing, or in patients who are not involved in excessive overhand motion but who have an anatomic predisposition to TOS, repetitive stress can lead to symptoms of TOS, and anatomical variants such as a cervical rib can cause narrowing of the scalene triangle, and other possible sources of compression include anomalous first rib, C7 transverse process, or post-traumatic changes from prior clavicular or rib fractures, and during extreme shoulder abduction, the costoclavicular space is naturally narrowed, and the costoclavicular triangle consists of the clavicle superiorly, the anterior scalene muscle posteriorly, and the first rib inferiorly, and all three neurovascular structures pass through this space, and narrowing of this space tends to cause venous symptoms, frequently denoted venous TOS (vTOS), with varying degrees of additional symptoms due to arterial or brachial plexus compression, and the interscalene triangle consists of the anterior scalene muscle, middle scalene muscle, and first rib, and trunks of the brachial plexus and the subclavian artery pass through this space, and narrowing here causes neurological dominant TOS (nTOS), arterial dominant (aTOS), or combinations of both, and the pectoralis minor space, defined by the pectoralis minor muscle anteriorly and chest wall posteriorly, is essentially an extension of the thoracic outlet and can result in varying degrees of compression similar to the costoclavicular space 1. CTV may be performed in the postintervention setting to evaluate interval changes in the thoracic outlet, assess adequate decompression, and follow up on vessel patency or complications, and recurrent or persistent venous thrombosis may require reintervention, and in the postoperative setting, a new symptom may indicate a complication, and consultation with a radiologist may be useful at the time of examination ordering to optimize the study for the prevailing clinical symptom, and this document has separated imaging appropriateness based on neurogenic, arterial, or venous symptoms, acknowledging that some patients may present with combined symptoms that may require more than one study to fully resolve, and understanding the various anatomic spaces, causes of narrowing, and resulting neurovascular changes are important in choosing and interpreting radiological imaging, which may be performed to help diagnose TOS and plan for intervention, and the gold standard method for CRVT diagnosis is venography, but it is invasive and requires exposure to intravenous contrast and radiation, and the preferred method for CRVT screening is ultrasonography, and CRVT is usually treated with anticoagulation, and initial anticoagulation treatment usually involves low molecular weight heparin, followed by vitamin K antagonists, except in patients with cancer and patients with poor oral absorption, for whom low molecular weight heparin is preferred, and the length of time a patient should be anticoagulated will depend on individual case characteristics (risk factors, extent and characteristics of the thrombus, catheter removal) but generally is 3-6 months and in some cases forever, and the decision to remove or maintain the catheter will be based on each individual situation, and removal is generally warranted when HPN is no longer necessary, if it is infected or occluded, if there is contraindication to anticoagulation treatment, or if there are persistent symptoms and signs despite anticoagulation, and thrombolysis works by activating plasminogen to plasmin, which breaks down fibrin clots, restoring blood flow and preventing long-term venous damage, and early intervention is crucial as it leads to better outcomes and lower rates of post-thrombotic syndrome, and after successful thrombolysis, patients typically undergo thoracic outlet decompression surgery (first rib resection) within 1-3 months, followed by anticoagulation therapy for at least 3 months, and contraindications include recent major surgery, active bleeding, stroke within 3 months, or pregnancy, and the standard approach involves catheter-directed thrombolysis using agents such as alteplase (tPA) at doses of 0.5-1.0 mg/hour for 24-48 hours, with concurrent heparin infusion (500-1000 units/hour), and lysis should be performed before any surgical decompression to restore venous patency and reduce post-thrombotic syndrome risk, and thrombolytic agents are not usually employed in upper limb thrombosis, except in cases of massive thrombosis with severe symptoms and signs, if the bleeding risk is low and the thrombus is recent (less than ten days long), and in some cases, it may be necessary to place a superior vena cava filter if there is contraindication to anticoagulant treatment, if the thrombus progresses despite anticoagulation, or if there is a symptomatic pulmonary thromboembolism despite anticoagulation, and catheter mechanical interventions (aspiration, fragmentation, thrombectomy, balloon angioplasty, or stenting) or surgical procedures (thrombectomy, venoplasty, venous bypass, or decompression at the venous thoracic outlet) are also options to consider in certain cases 1.

From the Research

Indications for Thrombolysis in Venous Thoracic Outlet Syndrome (VTOS)

Thrombolysis is indicated for patients with VTOS who have acute venous thrombosis of the axillo-subclavian vein. The decision to perform thrombolysis is based on several factors, including:

• The presence of acute venous thrombosis 2
• The severity of symptoms 2
• The presence of underlying anatomical abnormalities 3

Treatment Approaches

Treatment approaches for VTOS may include:

• Anticoagulation [(4,2)]
• Catheter-directed thrombolysis [(2,3,5)]
• Surgical decompression [(2,3,6)]
• Endovascular interventions, such as angioplasty and rheolytic thrombectomy [(3,5)]
• Percutaneous mechanical thrombectomy 5

Timing of Thrombolysis

The optimal timing of thrombolysis in VTOS is not well established. However, studies suggest that early diagnosis and treatment can improve symptoms and quality of life 2. In some cases, thrombolysis may be performed immediately after diagnosis, while in other cases, it may be delayed until after surgical decompression 5. The median time from endovascular intervention to rib resection was 14 days in one study 3.