Internal Jugular Vein Thrombosis

Etiology

A German physician, Rudolf Virchow is the first ever to coin the term of thrombosis and pulmonary embolism in 1855. The Virchow Triad refers to hypercoagulability, stasis or turbulence in blood flow and endothelial dysfunction. Despite being flushed with anticoagulants such as heparin, catheter placement in the internal jugular vein not only causes changes in the blood flow but also causes injury to the endothelium of the vein. In a retrospective review by Major KM et al. showed that the presence of a central venous catheter was a significant factor for IJV thrombosis.[3] However, there are various causes of the IJV such as Inherited hypercoagulable states, including Factor V Leiden mutation, Protein S deficiency, Protein C deficiency, Antithrombin deficiency, acquired risk factors including previous thromboembolism, malignancy, pregnancy, oral contraceptives, an intravenous drug, trauma, immobilization. Additionally, jugular vein suppurative thrombophlebitis, also known as Lemierre syndrome is suspected in patients with persistent bacteremia preceded by pharyngitis, dental infections or infectious mononucleosis. There have also been reports of surgical complications to the neck, necrotizing fasciitis, antiphospholipid syndrome, nephrotic syndrome, and severe burns.

Epidemiology

A cross-section study suggested that the most common causes of internal jugular vein thrombosis are cancer and central venous catheter.[4] A systematic review and meta-analysis revealed 7.5 percent of patients out of 5636 cancer patients developed catheter-related venous thrombosis.[5] In examining catheter-related venous thrombosis, researchers weighed many factors such as the previous history of deep vein thrombosis, insertion site, and positioning of the catheter tip. Patients with factor V Leiden or other hypercoagulopathy were found to have a threefold increased risk of developing upper extremities thrombosis.

Pathophysiology

The pathogenesis of venous thromboembolism (VTE) is Virchow triad. Three components of Virchow triad as below,

• Vascular endothelial injury, such as atherosclerosis, central venous catheter placement, vascular inflammation, trauma, severe burn
• Change of blood flow, such as immobility, arrhythmia, venous mechanical obstruction 
• Hypercoagulopathy, such as thrombophilia, malignancy, nephrotic syndrome, pregnancy, hormone therapy

Internal jugular vein thrombosis is most commonly due to prolonged central venous catheterization, trauma to the neck, infection, ovarian hyperstimulation syndrome (OHSS) and intravenous drug abuse.

History and Physical

Internal jugular vein thrombosis is asymptomatic in the majority of patients. Due to its subtle manifestation, it is difficult to diagnose for clinicians. However, patients may present with typical signs for deep vein thrombosis such as erythema, tenderness, and warmth. On physical examination, swelling at the left sided neck, mandible angle or the anterior border of the sternocleidomastoid muscle can be found. Internal jugular vein thrombosis in the setting of infection as known as Lemierre syndrome (necrobacillosis), fever, headache, swelling of the neck and angle of the jaw along with trismus is another possible presentation.

Evaluation

Laboratory studies may show an increased level of D-dimer, a degradation product of fibrin that is highly sensitive and nonspecific for venous thrombosis. Elevated levels of D-dimer present in malignancy, sepsis, recent surgery or trauma, pregnancy which often coexist with internal jugular vein thrombosis. Compression ultrasonography with Doppler is the test of choice for diagnosis with a sensitivity of 96% and a specificity of 93%.[6] While venography is the gold standard for diagnosing the IJV thrombosis, bedside ultrasound is noninvasive and rapid which may show hyperechoic thrombus within the IJV. CT scan may indicate an intraluminal filling defect in the jugular venous wall. CT scan may be superior to ultrasound due to a better assessment of veins located under soft tissues.

Treatment / Management

The risk of bleeding requires careful assessment. Anticoagulation therapy is individualized for each patient; tools such as HAS-BLED help assess the bleeding risk in adults[7] However, no definitive index or tool can reliably predict bleeding risk in patients with internal jugular vein thrombosis. In patients with an indwelling catheter, it is crucial to remove the catheter; however, if the catheter cannot be removed for any reason, then anticoagulants should be initiated. Patients without bleeding risks should receive dual therapy with low molecular weight (LMW) heparin and warfarin, dual therapy with LMW heparin followed by direct thrombin inhibitor or factor Xa inhibitor, or monotherapy with factor Xa inhibitor. For high-risk patients like thrombophilia, some studies have suggested an INR maintained between 2.5 and 3.0; long-term warfarin therapy can also be a consideration. However, clinical studies in anticoagulation therapy for IJV thrombosis are lacking. Internal jugular vein thrombosis is often found incidentally in the majority of the patients. Hence, many patients were left untreated. Intravenous thrombolytic infusion regimens such as alteplase have been reported to be effective in IJV thrombosis. For patients diagnosed with catheter-induced IJV thrombosis, thrombolysis is not recommended as first-line therapy, as there is sparse evidence to suggest that thrombolysis leads to better outcomes than anticoagulation. Rarely do patients need surgical interventions.

Differential Diagnosis

The clinical manifestations that accompany internal jugular vein thrombosis include erythema, swelling, and warmth along the sternocleidomastoid muscle resemble neck infections such as cellulitis. Facial pain, neck edema, a palpable cord, and neck fullness can present in some patients and may be similar to superior vena cava syndrome. A mechanical obstruction such as a lung tumor should be ruled out. 

• Mediastinitis 
• Superior vena cava syndrome
• Malignancy 

Prognosis

In a prospective study, the mortality rate of internal jugular vein thrombosis was reported to be 44%. The mortality rate is significantly higher in patients over 75 years old, patients not treated with anticoagulation and patients with an indwelling central venous line.  In patients with underlying comorbidities such as malignancy, chronic kidney diseases, infections, and multiorgan failure, mortality is significantly higher.

Complications

Pulmonary embolism is the most common complications in upper extremity thrombosis, followed by post-thrombotic syndrome and death.[8] Complications of IJV thrombosis are pulmonary embolism (10.3%) and post-thrombotic syndrome (41.4%).[4] In Lemierre's syndrome, without proper antibiotic management, 97 percent of cases developed septic emboli to the lung.[9]