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Unprovoked internal jugular vein thrombosis: a case report and literature review
Thrombosis Journal volume 19, Article number: 2 (2021)
Managing thrombosis in rare sites is challenging. Existing studies and guidelines provide detailed explanations on how to overcome lower-limb thromboses and pulmonary embolisms, but few studies have examined thrombosis in rare sites. Lack of data makes clinical practice heterogeneous. Recommendations for diagnosing, treating, and following-up internal jugular vein thrombosis are not clearly defined and mostly based on adapted guidelines for lower-limb thrombosis.
A 52-year-old Caucasian woman came to the Emergency Department with chest, neck, and left arm pain. Computed tomography imagery showed a left internal jugular vein thrombosis. An extensive workup revealed a heterozygous factor V Leiden gene. Therapy was initiated with intravenous unfractionated heparin, then switched to oral acenocoumarol, which resolved the symptoms. Based on this case presentation and a literature review, we summarize the causes, treatment options, and prognosis of unprovoked internal jugular vein thrombosis.
Managing internal jugular vein thrombosis lacks scientific data from large randomized clinical trials, partly because such thromboses are rare. Our literature review suggested that clinical treatments for internal jugular vein thrombosis often followed recommendations for treating lower-limb thrombosis. Future specific studies are required to guide clinicians on the modalities of diagnosis, screening for thrombophilia or oncologic disease, treatment duration, and follow-up.
Thromboembolic disease is the third most frequent cardiovascular disease . It has been thoroughly studied in recent decades, resulting in a standard diagnostic strategy, international guidelines, and new medications [2, 3].
There is scarce medical literature available on unprovoked internal jugular vein (IJV) thrombosis, essentially just case reports and short case series. IJV thrombosis is, therefore, often managed with reference to guidelines dedicated to thromboses occurring in more common sites, notably the deep veins of the lower limbs [2, 3]. Yet unusual thrombosis sites are associated with distinct risk factors and complications, and some treatments (e.g. direct oral anticoagulants) have not been tested specifically. Thus, we believe that specific recommendations are needed to guide the treatment management of patients with thromboses in uncommon sites.
This report describes a case of unprovoked IJV thrombosis and an accompanying literature review about diagnosing and treating this condition.
A 52-year-old Caucasian woman under treatment for hypothyroidism arrived at the Emergency Department with constrictive chest pain that had been radiating into her left arm and cervical region for 1 week, accompanied by new-onset dyspnea which had worsened 2 days before her medical visit. Her physical examination was unremarkable, except for high blood pressure (188/104 mmHg) and excess weight (body mass index = 28 kg/m2); a blood test showed a high D-dimer concentration (2170 μg/l). A computed tomography (CT) scan performed to exclude pulmonary embolism was inconclusive. However, fat infiltration around the left jugular-carotid led to a further investigation using neck ultrasound. This showed a thrombosis emerging from the base of the left subclavian vein and extending 11 centimeters into the IJV, sparing the cerebral vessels.
The patient described spontaneous hair loss and a 10 kg gain in weight over the previous year. She was taking levothyroxine but took no other medication or hormonal substitutes. There was no history of smoking, recent surgery, trauma, infectious disease, intravenous medical or recreational drug use, or past catheter insertion.
A chest CT scan and a colonoscopy revealed no cancer. A recent gynecological check-up consisting of a physical examination, a mammography, and a Pap smear found no pathology. A thyroid-stimulating hormone test and urinary cortisol were normal. Because of the patient’s young age and no obvious risk factor for thromboembolic disease, we completed the investigations with a thrombophilia workup. Antinuclear antibodies were positive at 1:320, but without other criteria suggesting overt lupus . Otherwise, antinucleoprotein antibodies (SSA, SSB, RNP, Sm, Scl70, Jo1), antinucleosome antibodies, anticardiolipin antibodies, and anti-B2-glycoprotein antibodies were negative. We did not test for lupus anticoagulant due to the patient’s anticoagulation treatment and the risk of a false-positive . Antithrombin, protein C, and protein S activity were within the normal ranges and were tested before the introduction of anticoagulant treatment. Only a heterozygous factor V Leiden gene (R506Q) was found positive. We concluded on the diagnosis of an unprovoked IJV thrombosis.
After 5 days of intravenous unfractionated heparin, symptoms rapidly regressed, allowing a switch to an oral anticoagulant (acenocoumarol). The patient was discharged home 1 week after admission. After 3 months, the decision to continue anticoagulation with acenocoumarol was taken according to European Society of Cardiology guidelines  for patients over 50 years old with unprovoked thrombosis and a low risk of major bleeding (HAS-BLED score for major bleeding risk = 1 due to hypertension, corresponding to a 3.4% risk ). 6 months after Emergency Department admission, the patient was symptom-free.
Discussion and conclusions
We have described a patient presenting with unprovoked IJV thrombosis, heterozygous factor V Leiden gene, and no other obvious risk factors. This rare thrombosis site reveals the limits of international guidelines based on large, randomized clinical trials mainly designed for deep-vein thrombosis in a limb or pulmonary embolism. There is, therefore, a lack of evidence which might guide clinicians in their workup and treatment of thrombosis in rare sites. Although, by their very nature, published case reports and case series provide biased information, exploring similar cases can be a first step (and sometimes the only one possible) towards collecting scientific evidence.
Medline research strategy
We searched Medline using the keywords (spontaneous OR unprovoked OR idiopathic OR primary AND internal jugular vein thrombosis AND English) and excluded reports of provoked IJV thrombosis to collect information on causes, treatment modalities, and complications. We retrieved 40 relevant articles in English (Table 1). These articles included 48 patients with unprovoked IJV from 17 countries, but mostly from Japan (9/40 articles). More than a third (17/48; 35%) were still truly idiopathic after the workup (Table 2).
Internal jugular vein thrombosis epidemiology
Upper-limb thrombosis accounts for a maximum of 10% of all deep-vein thromboses [2, 47]. IJV thrombosis is even less frequent, but epidemiological studies are lacking (other unusual sites for thrombosis, such as the mesenteric vein, account for 0.002–0.006% of all inpatient admissions) . Overall, the most common causes of IJV thrombosis are cancer, central venous catheter placement, and ovarian hyperstimulation syndrome (OHS) . IJV thrombosis can be provoked or unprovoked. The former accounts for four out of five cases . Most IJV thromboses are secondary to central catheter or pacemaker placement, extrinsic compression (by a tumor or malformation), local infections (e.g., Lemierre disease), cervical trauma, or ENT cancer. Unprovoked IJV thrombosis is uncommon and has been associated with paraneoplastic disease, thrombophilia, OHS, and idiopathic IJV [10, 26, 49,50,51]. OHS is associated with thromboembolic complications, but their mechanisms are incompletely understood . In addition to the usual hemostatic changes during pregnancy , OHS can cause increased levels of coagulation factors .
The spectrum of potential clinical presentations is broad, ranging from asymptomatic disease to diffuse and non-specific pain. Neck pain and swelling are the most frequent symptoms, found in 24/48 patients (50%). IJV thrombosis is a serious event, with a potentially fatal outcome, but complications in IJV thrombosis have seldom been reported . Pulmonary embolism was reported in 3 cases (6%). Surprisingly, there were no cases describing neurological complications. The risk of recurrent IJV thrombosis is unknown since the follow-up of published cases was generally interrupted after 3 to 6 months (Table 1).
D-dimer concentrations have excellent negative predictive value, even for deep-vein thrombosis of the upper extremities. However, D-dimer concentrations have not been validated with IJV thrombosis because of the lack of prospective outcome trials. Lower D-dimer sensitivity in IJV thrombosis could be an issue, resulting in higher false-negative rates, which could lead to fatal consequences [56, 57].
Performance of imaging to diagnosis IJV is unknown. The majority of reports used ultrasonography often completed with CT (21/48; 43.8%). In cases of unprovoked IJV thrombosis, oncological disease and thrombophilia should be screened for since they are more common than in cases of lower-body thrombosis. Indeed, these conditions are frequently associated with IJV thrombosis (Table 2).
Thrombophilia is defined as a hereditary or acquired genetic abnormality predisposing the patient to thromboembolic events . The F5 R506Q gene (the factor V Leiden mutation) is the most common pro-thrombotic gene mutation in Caucasians , affecting 3–7% of this population. It is a gain-of-function mutation in the procoagulant factors. The annual incidence of venous thromboembolism (VTE) in heterozygous carriers of the factor V Leiden mutation is approximately 0.45% .
Middeldorp et al. recommended not routinely screening for hereditary thrombophilia as it does not affect most patients’ clinical management, and long-term anticoagulation is generally recommended for patients with unprovoked thrombosis . Thrombophilia screening is only recommended for young (age < 50) patients with a VTE, in cases of recurrent VTE, and in cases involving a family history of VTE . Hereditary thrombophilia does not significantly increase the risk of recurrence (relative risk from 1.4–2.5, depending on the type of mutation ), and anticoagulation treatment should be stopped after 3 months in the absence of risk factors such as cancer. American guidelines also propose anticoagulation cessation after 3 months . European guidelines propose individual assessments of the risks of recurrence and major bleeding in order to decide on whether anticoagulation treatment should continue . In the present case, we chose to screen for thrombophilia and cancer because the thrombosis was unprovoked and located in an unusual site. The patient’s borderline age was also taken into account in accordance with an algorithm proposed by Connors .
In our review, only 8% (4/48) of patients with IJV thrombosis had an inherited coagulopathy, a low prevalence also seen among Caucasians if patients from Japan, Sri Lanka, India, Jordan, Israel, Turkey, and Saudi Arabia are excluded from the review. Paraneoplastic disease was far more common than inherited coagulopathy, affecting one third of patients (16/48). Thus, an active workup for oncological diseases is of the utmost importance in unprovoked IJV thrombosis.
Treatment of IJV thrombosis
There are no specific guidelines for the treatment of IJV thrombosis. Treatment is often based, by analogy, on guidelines [2, 3] for upper-limb thrombosis (Tables 1 and 3). Initial treatment (5–21 days following diagnosis) consists of parenteral therapy with low molecular weight heparin (or unfractionated heparin) with a transition using vitamin K antagonists. The alternative therapy for non-cancer patients is high-dose direct oral anticoagulants. Treatment duration is at least 3 months, with possible long-term anticoagulation depending on the cause of thrombosis . To date, no randomized clinical trials have evaluated anticoagulation for upper extremity deep-vein thrombosis. The only ongoing research is a prospective clinical study assessing oral apixaban for the treatment of upper extremity deep-vein thrombosis (including IJV thrombosis). However, to the best of our knowledge, no results have been published yet . The majority of cases in our literature review used unfractionated heparin (26/40; 65%), usually in association with an oral anticoagulant (19/40; 47.5%). Treatment duration varied from 2 weeks to 6 months for non-paraneoplastic cases (Table 3).
Follow-up of IJV thrombosis
No specific guidelines exist for IJV thrombosis follow-up. Gbaguidi et al. used a venous ultrasound scan at three and 6 months. Boedeker et al.  proposed an ultrasound scan each month until 6 months of follow-up.
The management of internal jugular vein thrombosis is heterogenous and currently based on the management of lower extremity deep-vein thrombosis, with a low rate of complications. The lack of guidelines and large series means that the modalities of diagnosis and treatment type and duration are variable. Given the low prevalence of IJV thrombosis, large, randomized studies would be hard to carry out. Data from our literature review suggest that treatments could tend towards those used for lower limb deep-vein thrombosis, but that the modalities of diagnosis and the duration of treatment and follow-up should be clarified.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
Acute respiratory distress syndrome
Bowel inflammatory disease
Chronic obstructive pulmonary disease
Ear, nose, and throat
Internal jugular vein
Antihistidyl transfer-RNA synthetase antibodies
Magnetic resonance imaging
Non-small cell lung cancer
Ovarian hyperstimulation syndrome
Anti-Sjögren’s syndrome type A antibodies
Anti-Sjögren’s syndrome type B antibodies
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Payrard, L., Iten, L., Donzé, J. et al. Unprovoked internal jugular vein thrombosis: a case report and literature review. Thrombosis J 19, 2 (2021). https://doi.org/10.1186/s12959-020-00246-7
- Internal jugular vein