Upper extremity deep vein thrombosis ( UEDVT) refers to thrombosis within the subclavian vein, internal jugular vein, trunk veins of the head and arm, and deep veins of the upper extremity, such as axillary, brachial, radial, and ulnar veins, with axillary and subclavian vein thrombosis being the most common. Its serious consequences, like those of lower extremity DVT, include pulmonary embolism, post-thrombotic syndrome, vascular occlusion, and superior vena cava syndrome. In patients with DVT, upper extremity DVT accounts for 5%, l1%, and 14%; and in hospitalized patients, the incidence of upper extremity DVT is 0.15% and 0.2%. However, clinicians know little about it, so this paper reviews the progress of diagnosis and treatment of upper limb deep vein thrombosis in recent years.
1, Risk factors
The risk factors for primary UEDVT are mainly hereditary propensity to thrombosis and abnormal thoracic outlet anatomy, accounting for about 20%. The risk of UEDVT increases 5-6-fold with protein C, protein S or antithrombin, coagulation factor III deficiency, or with mutations in coagulation factor V Leiden and prothrombin G202IOA. Mutations in proteins or coagulation factors lead to a hypercoagulable state of blood and are an important cause of inherited propensity to thrombosis.
Abnormalities of the thoracic outlet anatomy are most typical in Paget-Schroetter syndrome, hence the name thoracic outlet syndrome, and are commonly seen in weightlifters, wrestlers, throwing sports athletes, blacksmiths, painters, auto mechanics, and other people with repetitive upper arm supination movements.
Secondary UEDVT accounts for about 80% of cases, with two common risk factors, central venous line placement and tumor, and other rare factors such as pacemaker defibrillator implantation, previous history of deep vein thrombosis, hospitalization for more than 10 d, age greater than 65 years, history of surgery or upper extremity braking within 30 d, chemotherapy and radiation therapy, smoking, and concomitant diseases such as diabetes mellitus and hypertension.
The RIETE study showed that central venous cannulation was the strongest independent risk factor for UEDVT, with a 7-fold increase in incidence compared to those without central venous cannulation. The incidence of UEDVT is influenced by the punctured vein, the unheparinized process of placement, repeated punctures and placements in the same vessel, the diameter of the catheter, and the location of the tip. The subclavian vein was preferred for short-term (<1 month) central venous placement; for long-term placement (>1 month), the risk of complications was similar for subclavian and internal jugular vein catheters. The risk of short-term placement of internal jugular and femoral veins was similar. Triple-lumen catheters have a 20-fold higher risk of UEDVT than single-lumen catheters.
Tumor is another important risk factor, with 38% of UEDVTs noted to be associated with malignancy in the RIETE study, and another multicenter study reported similar results. Lung cancer was the most common (28%), the rest were breast tumors (15%) and colorectal tumors (13%).
2 .Clinical characteristics
Lack of typical symptoms, swelling of the affected limb is mostly found after physical examination (80%). 30%-50% of patients have pain in the affected limb, erythema of the affected limb, superficial varicose veins, limb dysfunction, etc. are rare. 5% of patients have no symptoms. Patients often start with complications: ① pulmonary embolism is less common than lower extremity, the incidence is 9%; ② recurrence of deep vein thrombosis, the recurrence rate of thrombosis within 1-6 months is 1.7 times higher than that of lower extremity deep vein thrombosis, 6 months is the peak period, more than in situ recurrence; ③ post-thrombotic syndrome ( post-thrombotic syndrome, PTS): the incidence is 2%, axillary vein, subclavian vein thrombosis is more likely lead to the occurrence of post-thrombotic syndrome.
3. Auxiliary tests
3.1 D-dimer (D-dimer)
D-dimer has diagnostic value for pulmonary embolism and lower extremity deep vein thrombosis, but little research has been done on upper extremity deep vein thrombosis. Using 500 μg/L as the diagnostic value of D-dimer and controlling Doppler ultrasound diagnosis, 15 cases (29%) were positive in 52 cases of suspected upper limb DVT, with 100% sensitivity, 14% specificity, 32% positive predictive value, and 100% negative exclusion value.
3.2 Ultrasound (US)
Pressurized ultrasound determines the compressibility of the vessel wall, and color Doppler examines the intravascular blood flow signal. The sensitivity of pressurized ultrasound in diagnosing upper extremity deep vein thrombosis is 97%, and the specificity is 96%. The presence of intravascular thrombosis is determined when there is a change in vessel diameter, pathologic echogenicity, loss of vessel compressibility, lack of intravascular color signal, or a filling defect. The presence of incompressibility of the vessel alone is indicative of thrombosis. Color Doppler is usually used in veins where pressurized ultrasound is not available, such as the middle subclavian vein, inferior vena cava, and some cephalic trunk veins, with a sensitivity of 84% and specificity of 94%.
3.3 Venography (CV)
The gold standard for diagnosis, imaging signs are intravenous filling defects. Disadvantages: invasive, requires contrast. Cannot be performed in approximately 20% of individuals due to poor renal function, poor angiographic imaging, or contrast allergy. Only for cases in which the diagnosis cannot be confirmed by noninvasive examination but is highly suspected clinically.
3.4 CTV, MRI
MRI has a sensitivity of 71% and specificity of 89% for plain scan and 89% and 90% for enhanced, but the results are controversial.The diagnostic sensitivity and specificity of CTV and MRV for the diagnosis of upper extremity DVT are not available.Only 91.5% sensitivity and 94.8% specificity have been reported for the diagnosis of lower extremity DVT.CT and MR can also detect risk factors, such as CT and MR can also detect risk factors such as abnormal thoracic outlet anatomy, tumor, etc.
4.Diagnosis
UEDVT should be alerted to the presence of risk factors, especially when multiple risk factors coexist. the clinical symptoms of UEDVT are scored as follows: central venous invasive manipulation, +1 point; local pain, +1 point; unilateral limb edema, +1 point; other possible diagnoses, -1 point. A total score of -1-0, UEDVT is low probability; 1 is probable; 2-3 is very high probability. This score has a low diagnostic sensitivity and still needs to be combined with other laboratory tests. Ultrasound is preferred, combined with D-dimer examination. In patients with high suspicion but negative ultrasound, intravenous angiography is chosen.
5. Treatment
There is a paucity of research data on the treatment of upper extremity deep vein thrombosis. Primary UEDVT requires individualized treatment with anticoagulation, thrombolysis, and corrective surgical procedures such as clavicle or first rib resection with rhomboidectomy. Depending on the duration and severity of symptoms, thrombolysis is chosen within 14 d. The efficiency of thrombolysis decreases beyond 14 d. Those with failed thrombolysis and severe symptoms were treated with venous reconstruction, while those with mild or no symptoms were treated with first rib resection. Even if thrombolysis is successful or incomplete, the first rib resection must be performed. Anticoagulation should be continued for 3-6 months.
The treatment of secondary UEDVT is referred to pulmonary embolism and lower extremity deep vein thrombosis and is divided into an acute phase and a long-term treatment. The acute phase refers to the first 3 months after the diagnosis of thrombosis and aims to stop the progression of thrombosis and vascular occlusion. Interventional treatment can reduce the incidence of post-thrombotic syndrome and thrombotic recurrence. Long-term treatment refers to the stage after the acute phase treatment, the aim is to control the risk factors of thrombosis and the treatment of complications.
5.1 Anticoagulation
The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (ACCP) recommends: treatment of upper extremity DVT is the same as lower extremity DVT, with anticoagulation alone recommended, anticoagulation with low molecular heparin and sulforaphane immediately after diagnosis, anticoagulation for ≥3 months in patients with thrombosis in axillary and more proximal veins, CVC-associated UEDVT, tumor, and UEDVT unrelated to CVC and tumor Anticoagulation time of 3 months. Thrombotic recurrence rate after anticoagulation is about 0-4%.
5.2 Thrombolysis
Because of the lack of data from studies that thrombolysis can reduce the incidence of post-thrombotic syndrome and DVT recurrence, it is not used as first-line treatment for UEDVT. ACCP recommends it only for those with severe symptoms, thrombus occupying most of the subclavian and axillary veins, thrombosis within 14 d, good limb function, life expectancy longer than one year, and low risk of bleeding. Guidelines do not yet recommend a specific dose, and the success rate of first thrombolysis is approximately 72%-91%. Thrombolysis of thrombi beyond 2 weeks is often ineffective, and catheter thrombolysis is safer than intravenous thrombolysis. Further studies are needed to confirm the risks and long-term benefits of thrombolysis. Anticoagulation is also required in patients after thrombolysis.
5.3 Surgical Thrombectomy
For patients with large thrombus formation affecting limb function or with absolute contraindications to anticoagulation or thrombolysis.
5.4 Superior vena cava filter
The superior vena cava is short, making the placement of a filter difficult. The incidence of fatal complications is 3.8%, including cardiac tamponade and aortic perforation, and the rate of use is extremely low. It is only indicated for patients in whom anticoagulation is contraindicated or has failed, and more research data are needed to confirm its effectiveness and safety.
5.5 Angioplasty and endovascular stenting
No study data on indications and long-term follow-up are available. Clinical data suggest repeated interventions, which can increase the risk of thrombosis, but reliable study data are lacking.
5.6 Removal of central venous cannulae
The need for removal of a central venous line is controversial; both the 2010 International Society on Thrombosis and Haemostasis (ISTH) guidelines and the 2012 ACCP recommend that a central venous line may remain in place if upper extremity deep vein thrombosis has occurred and treatment still requires retention of a central venous line, provided it is accompanied by anticoagulation. If treatment by central venous placement is not required then removal is recommended. Long-term anticoagulation (≥3 months) is required after removal of the tube in oncology patients and 3 months in non-oncology patients.
5.7 Elastic stockings and elastic bandages
They are prohibited for symptomatic patients and are only used to relieve symptoms in PTS patients.
6 .Prevention
There are few studies on prevention of upper extremity DVT. Central venous placement is an independent risk factor, so choosing smaller diameter catheters and long-term placement preferably in the subclavian and internal jugular veins can effectively reduce the incidence of UEDVT. Prophylactic use of low-dose low molecular heparin, warfarin, and vitamin K antagonists may reduce the recurrence of upper extremity DVT. Long-term anticoagulation is not yet supported by additional data, but ISTH, ACCP recommends 3-6 months of anticoagulation for patients with central venous placement, oncology patients, thoracic outlet syndrome, and post-thrombotic syndrome.
With more studies, we recognize that the clinical presentation, diagnostic methods and risk factors of upper extremity DVT are different from those of lower extremity DVT, but both have similar complications and similar current management strategies, with anticoagulation being the mainstay. With the widespread use of invasive therapies, upper extremity DVT requires further in-depth study, and more research is needed in the future to support its clinical diagnosis and treatment.