Question 20

a)    List the risk factors, clinical features and relevant investigations for occlusive upper limb deep venous thrombosis (ULDVT) in critically ill patients.    (50% marks)

b)    Discuss the available management options.    (50% marks)

[Click here to toggle visibility of the answers]

College answer


Risk factors: (20% Marks)

  1. Catheter Insertion
    1. Size /number of lumens increases risk
    2. Position – PICC > Central
    3. Malposition of catheter
    4. Difficulty in placement
    5. Irritant infusion – e.g. TPN, Chemotherapy
    6. Catheter infection
  2. Systemic Conditions
    1. Malignancy
    2. Upper limb trauma
    3. Hypercoagulable state
    4. Previous thrombosis Marking Guide: 8-10 correct  2 marks

5-7 correct          1 mark

<5 correct           0.5 mark

Clinical Features: (20% Marks)

  1. May be asymptomatic
  2. Symptoms: discomfort, pain, paraesthesia and weakness
  3. Signs:
    1. limb swelling, oedema, venous collaterals
    2. Superior vena cava syndrome; oedema of face, neck and upper torso; dyspnoea; syncope; positive Pemberton’s sign.

Investigations: (10% Marks)

Compression ultrasound is the diagnostic standard, with >95% sensitivity and specificity. (this detail not required)

Doppler and CT may be required to diagnosis intrathoracic/super vena cava (SVC) obstruction.



Treatment: (50% Marks)

Treatments aim to alleviate the symptoms, prevent thrombin propagation and pulmonary embolism, and prevent post-thrombotic syndromes.

  1. Anti-coagulation:
    • Initiate with unfractionated heparin infusion or low molecular weight heparin (preferred)
    • Followed by either low molecular weight heparin or oral anticoagulants for 3 to 6 months
  2. Thrombolysis:
    • Limited evidence
    • Catheter-directed thrombolysis is upper limb has extensive swelling and functioned impairment
  3. Mechanical catheter intervention:
    • Aspiration of the thrombus, fragmentation and thrombectomy should be considered in patients with persistent severe symptoms, despite anticoagulation or thrombolysis.
  4. SVC filters:
    • Evidence is lacking
    • Prevention of pulmonary embolism in patients with ULDVT in whom anticoagulation is contraindicated or thrombus progression despite anticoagulants.
    • Significant complications including cardiac tamponade and aortic perforations reported.
  5. Catheter/device removal:
    • No need for routine removal
    • Remove if infected
    • Factors to be considered include the ongoing need for the catheter and difficulty in venous access.

(Highlighted points in treatment section are required for a pass mark.)

Examiners Comments:

Topic was poorly understood, with little knowledge beyond superficial. It was suspected that that relates to poor exposure and experience of more advanced interventions (thrombolysis, possible radiology directed treatments). Little was mentioned around importance of lines in thrombosis and almost everyone who remembered wanted to pull the lines out without thought or consideration of the implications.


Risk factors for upper limb DVT from Kommareddy et al (2002):

Gene mutations

  • Factor V (G1691 A)
  • Prothrombin (G20210A) Methylene-tetrahydrofolate
    reductase MTHFR (C677T)
  • Protein C
  • Protein S
  • Fibrinogen
  • Antithrombin

Acquired thrombophilias

  • Cancer
  • Congestive heart failure
  • Pregnancy
  • Antiphospholipid syndrome Nephrotic syndrome
  • Liver disease
  • Disseminated intravascular coagulation
  • Sepsis
  • Heparin-induced thrombocytopenia
  • Vasculitic disorders
  • Inflammatory bowel disease

Other factors

  • Thoracic outlet syndrome
  • Strenuous effort
  • Central venous catheters
  • Implanted pacemakers
  • Trauma
  • Previous thrombosis
  • Antineoplastic agents
  • Oral contraceptives

Specific difference between upper limb and lower limb DVT risk factor profiles, according to Cote et al (2017)

  • Recent surgery was less common in the upper limb DVT patients (12% vs 18%)
  • Malignancy was more common (50% had a malignancy, vs 30%)
  • Age was less of a risk factor (younger patients developed upper limb DVTs), except where the upper limb clot was provoked by a catheter
  • Immobility was much less of a risk factor (19% vs 43% for lower limb DVT)
  • Oral contraception or hormone replacement therapy was twice as common among the upper limb DVT group (20% vs 9.2%)
  • Upper limb central lines were a major risk factor.

Clinical features:

  • Generic clinical features of DVT:
    • Pain
    • Limb swelling
    • Oedema
    • Paraesthesia
    • Cord-like structure on palpation
    • Redness due to phlebitis
    • Coolness due to poorer perfusion
    • Decreased mobility or dexterity of the limb
  • Features unique to upper limb DVT:
    • Neck stiffness
    • Facial swelling
    • Pemberton's sign (with SVC obstruction)
    • Failure to insert upper limb CVCs ("the catheter just won't thread")
  • There are also a few clinical features unique to catheter-associated DVTs:
    • Inability to withdraw blood from the catheter
    • Inability to inject into the catheter
    • Loss of transducer waveform


  • DSA or plain radiocontrast venography is the gold standard
  • Ultrasound is substituted in virtually every situation as a nontoxic noninvasive alternative
  • Imaging with CT venography is the main approach to diagnosis if ultrasound is not available or for some reason uninformative (eg. the patient is covered in burns dressings). Additionally, CT of the veins is often the only way to map the venous circulation of the mediastinum and the pelvis.
  • Impedance plethysmography (Hull et al, 1986) where the electrical impedance of the limb is measured with electrodes before and after cuff deflation
  • Molecular tracer imaging (Houshmand et al, 2014), where the patient is injected with a radioactive tracer which binds to the clot and reveals it on a scintigraphy scan (PET/CT).


Guidelines from the American College of Chest Physicians (Kearon et al, 2012) recommend the following anticoagulation regimen:

  • Isolated brachial vein thrombosis: 
    no anticoagulation unless symptomatic or associated with a CVC
  • Proximal, provoked by some significant factor, which is now gone:
    anticoagulant therapy for 3 months. 
  • Proximal and associated with malignancy:
    anticoagulant therapy for 3-6 months.
  • Proximal and associated with a central line:
    anticoagulant therapy for 3 months if you removed it;
    or, anticoagulant therapy until you decide to take it out.

In addition to this (not instead of it), one may need acute intervention:

  • Systemic thrombolysis (not recommended but is one of the options)
  • Regional thrombolysis (i.e. you pick a vein distal to the clot and inject a small amount of thrombolytic agent into it)- generally not recommended but is one of the options
  • Catheter-directed thrombolysis (where a central venous catheter is introduced into the clot from a distant site, and then used to infuse the clot with a thrombolytic agent) - not very popular since the ATTRACT trial (Vedantham et al, 2017) which demonstrated an increased risk of bleeding without much of an improvement in patient-centred outcomes
  • Surgical thrombectomy for patients in whom no other method is available
  • Vena cava filter placement is mentioned by the college in the management strategies for DVT, but this makes no logical sense as the filter itself does nothing to treat the DVT, unless one accidentally fragments the clot with their filter in the process of insertion. It is a risk mitigation strategy in patients who have failed anticoagulation or for whom anticoagulation is absolutely contraindicated.


Cook, Deborah, et al. "Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors." Critical care medicine 33.7 (2005): 1565-1571.

Miri, MirMohammad, Reza Goharani, and Mohammad Sistanizad. "Deep vein thrombosis among intensive care unit patients; an epidemiologic study." Emergency 5.1 (2017).

Wheeler, H. B. "Diagnosis of deep vein thrombosis. Review of clinical evaluation and impedance plethysmography." American journal of surgery 150.4A (1985): 7-13.

Williams, Michael T., et al. "Venous thromboembolism in the intensive care unit.Critical care clinics 19.2 (2003): 185-207.

Hirsch, Denise R., Edward P. Ingenito, and Samuel Z. Goldhaber. "Prevalence of deep venous thrombosis among patients in medical intensive care." Jama 274.4 (1995): 335-337.

Hong, Kee Chun, et al. "Risk factors and incidence of deep vein thrombosis in lower extremities among critically ill patients." Journal of clinical nursing 21.13-14 (2012): 1840-1846.

MAl-Dorzi, Hasan, and Yaseen M. Arabi. "Venous Thromboembolism in Critically Ill Patients: Risk Stratification and Prevention." Critical Care Update 2019 (2019): 29.

García-Olivares, Pablo, et al. "PROF-ETEV study: prophylaxis of venous thromboembolic disease in critical care units in Spain." Intensive care medicine 40.11 (2014): 1698-1708.

Obi, Andrea T., et al. "Validation of the Caprini venous thromboembolism risk assessment model in critically ill surgical patients." JAMA surgery 150.10 (2015): 941-948.

Ellis, Martin H., Yosef Manor, and Moshe Witz. "Risk factors and management of patients with upper limb deep vein thrombosis." Chest 117.1 (2000): 43-46.

Cote, Lauren P., et al. "Comparisons between upper and lower extremity deep vein thrombosis: a review of the RIETE registry." Clinical and Applied Thrombosis/Hemostasis 23.7 (2017): 748-754.

Kommareddy, Aruna, Michael H. Zaroukian, and Houria I. Hassouna. "Upper extremity deep venous thrombosis." Seminars in thrombosis and hemostasis. Vol. 28. No. 01. Copyright© 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.:+ 1 (212) 584-4662, 2002.

Hill, Stephen L., and Robert E. Berry. "Subclavian vein thrombosis: a continuing challenge." Surgery 108.1 (1990): 1-9.

Saber, W., et al. "Risk factors for catheter‐related thrombosis (CRT) in cancer patients: a patient‐level data (IPD) meta‐analysis of clinical trials and prospective studies." Journal of Thrombosis and Haemostasis 9.2 (2011): 312-319.

Kinnison, Malonnie L., et al. "Upper-extremity venography using digital subtraction angiography." Cardiovascular and interventional radiology 9.2 (1986): 106-108.

HULL, RUSSELL D., et al. "Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis: a randomized trial." Annals of Internal Medicine102.1 (1985): 21-28.

Houshmand, Sina, et al. "The role of molecular imaging in diagnosis of deep vein thrombosis." American journal of nuclear medicine and molecular imaging 4.5 (2014): 406.

Malato, Alessandra, et al. "The impact of deep vein thrombosis in critically ill patients: a meta-analysis of major clinical outcomes." Blood Transfusion 13.4 (2015): 559.

McKelvie, Penelope A. "Autopsy evidence of pulmonary thromboembolism." Medical journal of Australia 160.3 (1994): 127-128.

Tran, Huyen A., et al. "New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism." Medical Journal of Australia 210.5 (2019): 227-235.

Noyes, ADAM M., and John Dickey. "The arm is not the leg: pathophysiology, diagnosis, and management of upper extremity deep vein thrombosis." RI Med J 100 (2017): 33-36.

Kearon, Clive, et al. "Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines.Chest 141.2 (2012): e419S-e496S.

Watson, Lorna, Cathryn Broderick, and Matthew P. Armon. "Thrombolysis for acute deep vein thrombosis." Cochrane Database of Systematic Reviews 11 (2016).

Vedantham, Suresh, et al. "Guidance for the use of thrombolytic therapy for the treatment of venous thromboembolism." Journal of thrombosis and thrombolysis41.1 (2016): 68-80.

Vedantham, Suresh, et al. "Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis." New England Journal of Medicine 377.23 (2017): 2240-2252.

Comerota, Anthony J. "The current role of operative venous thrombectomy in deep vein thrombosis." Seminars in vascular surgery. Vol. 25. No. 1. WB Saunders, 2012.