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What is the best approach to treat an upper extremity DVT?

From: The Hospitalist, May 2009

by Julie Hollberg, MD

Case

A 45-year-old female with a history of cellulitis requiring peripheral inserted central catheter (PICC) line placement for intravenous antibiotics presents two weeks after line removal with persistent, dull, aching pain in her right shoulder and difficulty removing the rings on her right hand. The pain worsens with exercise and is relieved with rest. The physical exam reveals nonpitting edema of her hand. The ultrasound shows subclavian vein thrombosis. What is the best approach to treating her upper extremity deep venous thrombosis (UEDVT)?

Left-arm edema and erythema associated with an axillary vein thrombosis.

Background

DVT and pulmonary embolism (PE) have been subject to increased publicity recently, and both conditions are recognized as serious entities with life-threatening consequences. In fact, more people die annually from blood clots than breast cancer and AIDS combined.1,2 Still, the increased DVT and PE awareness is primarily focused on lower extremity DVT (LEDVT)), while UEDVT is thought of as a more benign entity. However, current data suggest that UEDVT is associated with equally significant morbidity and mortality.

UEDVT prevalence has increased in step with the increased use of central venous catheters (CVCs) and pacemakers. Although most patients present with pain, swelling, parathesias, and prominent veins throughout the arm or shoulder, many patients will not display any local DVT symptoms. For example, Kabani et al recently presented data for 1,275 patients admitted to the surgical ICU over a 12-month period. They found the incidence of UEDVT was higher than that of LEDVT (17% vs. 11%; P=0.11). They also determined that scanning all four extremities diagnosed more DVT than two-extremity scans (33% vs. 7%; P<0.001).3

While current medical literature has pushed for increased UEDVT attention, there is no consensus on its treatment. Recent American College of Chest Physicians (ACCP) guidelines addressed UEDVT treatment specifically and recommended analogous treatment to LEDVT with heparin and warfarin.4 This follows prospective studies that have shown patients with UEDVT and LEDVT have similar three-month clinical outcomes. The ACCP guidelines do not specifically recommend different treatment courses based on whether the UEDVT is catheter-related or not. Furthermore, while one might assume that removal of an associated catheter might reduce the treatment duration, there is limited data to support shorter courses in this scenario.

KEY Points

  • UEDVT risk factors include central venous catheters, malignancy, thoracic outlet syndrome or other anatomic abnormalities, previous DVT, “effort-related” activities, and hypercoagulable states.
  • A significantly increased mortality rate exists among people diagnosed with UEDVT.
  • UEDVT should be treated similarly to LEDVT: UFH or LMWH followed by warfarin for at least three months.
  • The ACCP recommends against the routine use of thrombolytics, angioplasty, stent placement, or surgery. Still, some patients may benefit from these approaches, so each patient should be considered individually.

Additional Reading

  • Kearon C, Kahn SR, Agnelli G, et al. Therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2008;133(6Suppl):454S-545S.
  • Bernardi E, Pesavento R, Prandoni P. Upper extremity deep venous thrombosis. Semin Thromb Hemost. 2006;32(7):729-736.
  • Munoz FJ, Mismetti P, Poggio R, et al. Clinical outcome of patients with an upper extremity deep vein thrombosis: results from the RIETE registry. Chest. 2008;133(1):143-148.

Review of the Data

Incidence: UEDVT is becoming more common secondary to increased interventions in the upper extremity (CVC, pacemaker), and is more easily recognized due to improvement in noninvasive ultrasound technology. UEDVT accounts for up to 10% of all DVT, with an incidence of approximately three per 100,000 persons in the general population.5-8 Because UEDVT can also be asymptomatic, it is believed that the incidence likely is higher than previously reported, but prospective data are lacking.

Risk factors: UEDVT is further categorized as either primary or secondary, depending upon the cause. First described in the late 1800s, spontaneous primary thrombosis of the upper extremity, or Paget-Schroetter syndrome, accounts for approximately 20% of UEDVT.9 Primary UEDVT includes both idiopathic and “effort-related” thrombosis. Effort-related thrombosis usually develops among young people after strenuous or repetitive exercise, such as pitching a baseball. Some hypothesize that effort-related thrombosis is related to a hypercoaguable state or anatomic abnormalities, although a specific cause, such as thoracic outlet syndrome, is found in only 5% of these cases.10,11

Secondary UEDVT characterizes thrombosis in which an endogenous or exogenous risk factor is present. Endogenous risk factors include coagulation abnormalities, such as antithrombin, protein C and protein S deficiencies; factor V Leiden gene mutation; hyperhomocysteinemia; and antiphospholipid antibody syndrome. Exogenous risk factors include CVC pacemakers, intracardiac defibrillators, malignancy, previous or concurrent LEDVT, oral contraceptives, some artificial reproductive technologies (women can develop ovarian hyperstimulation syndrome, which is associated with increased hypercoaguability), trauma, and IV drug use (especially cocaine).5,12-14

Clinical presentation and diagnosis: Swelling (80% of patients) and pain (40% of patients) are the most common UEDVT symptoms at presentation.2 Other clinical features include new, prominent veins throughout the shoulder girdle, erythema, increased warmth, functional impairment, parathesias, and non-specific feelings of arm heaviness or discomfort. Symptoms typically worsen with arm use and improve with rest and elevation.15 Patients with UEDVT related to CVC are more likely to be asymptomatic and may present only with PE.16 The differential diagnosis includes superficial phlebitis, lymphatic edema, hematoma, contusions, venous compression, and muscle tears.17

Contrast venography is the gold standard for the UEDVT diagnosis. However, it is more expensive and invasive than ultrasound, and thus serial compression ultrasound is now the standard test in UEDVT evaluation. Then again, contrast venography remains the test of choice in patients with high pre-test probability and negative ultrasound results.18,19

Prevention: Nearly 70% of secondary UEDVT is associated with a CVC.5 Further, CVC use is the most powerful predictor of UEDVT (adjusted odds ratio (OR), 9.7; 95% CI, 7.8 to 12.2).2 Despite the association between CVCs and UEDVT, anticoagulant prophylaxis is not recommended. Studies evaluating the results of 1-mg warfarin conflict and include small populations. Warfarin’s potential interaction with antibiotics and dosing variance based on nutritional intake logically prompted studies on the potential benefit of low-weight molecular heparain (LWMH); however, these studies have failed to show benefit.20,21

Colorado Rockies pitcher Aaron Cook had a pulmonary embolism during a 2004 game that was attributed to effort-related thrombosis of his right arm. He needed two surgeries and 12 months of rehab before returning to the mound.

Treatment: Recent ACCP guidelines recommend treating UEDVT patients with unfractionated heparin (UFH) or LMWH and warfarin, with an INR goal of 2 to 3 for at least three months depending upon the overall clinical scenario. Two small studies evaluating catheter-related thrombosis (15 patients in each trial) reported no subsequent embolic phenomenon.22,23 Some authors interpreted this data to mean UEDVT was not as morbid as LEDVT and, subsequently, that catheter-related UEDVTs require only one month of therapy. Since the small studies were published, the increasing incidence and relevance of UEDVT have become more widely recognized, and most authors are recommending three months of treatment.

Still, it’s important to note that there aren’t any published data directly comparing the one-month and the three-month anticoagulation therapies. The RIETE registry, which is the largest ongoing published registry of patients with confirmed DVT or PE, reports similar three-month clinical outcomes between those with UEDVT and LEDVT.

Small, single-center trials have shown that active intervention, such as thrombolysis, surgery, or multi-staged approaches are associated with increased vein patency and decreased rates of post-thrombotic syndrome.24,25 However, ACCP has withheld general recommendations for these interventions based on a lack of sufficient data to comment on their overall safety and efficacy, as well as comparable rates of post-thrombotic syndrome (15% to 50%) in studies that directly compared surgical and medical intervention. In fact, the ACCP recommends against interventional treatments unless the patient has failed anticoagulation therapy, has severe symptoms, and expertise is available.4

Superior vena cava filters are available at some centers for patients in whom anticoagulation is contraindicated, but efficacy data is limited. While the data for filter use in UEDVT is limited, its use should be considered in patients who have a contraindication to anticoagulation and remain high risk for UEDVT (e.g., prolonged central line placement).

Upper extremity DVT prevalence has increased in step with the increased use of central venous catheters and pacemakers. Although most patients present with pain, swelling, parathesias, and prominent veins throughout the arm or shoulder, many patients will not display any local DVT symptoms.

Complications: Post-thrombotic syndrome (PTS) is the most significant local complication of UEDVT. PTS characteristics are edema, pain, venous ulcers, and skin pigmentation changes, and it is the result of chronic venous insufficiency due to the clot. A meta-analysis of clinical studies on UEDVT noted that PTS occurs in 7% to 46% (mean 15%) of patients.26 One hypothesis for the wide range in frequency is the lack of clear diagnostic criteria for PTS.27 No clear beneficial treatment or prevention for PTS exists, but many recommend graduated compression stockings for the arm.

Residual and recurrent thrombosis are associated with increased PTS risk, which emphasizes the need for further study of interventional treatment because preliminary work has shown increased rates of vein patency in comparison to anticoagulants alone. Recurrent venous thromboembolism (VTE), another local complication, appears to occur less often than it does in patients with LEDVTs, but reaches 8% after five years of followup.28

PE is less common on presentation among patients with UEDVT when compared to patients with LEDVT, but when PE occurs, the three-month outcome is similar.3 PE appears to be more frequent in patients who have a CVC, with an incidence as high as 36% of DVT patients.4,13,21,29

Increased mortality: The mortality among UEDVT patients has been described as 10% to 50% in the 12 months after diagnosis, which is much higher than the ratio in LEDVT patients.21,30 This in part is due to sicker cohorts getting UEDVT. For example, patients with distant metastasis are more likely to develop UEDVT than those with confined malignancy (adjusted OR 11.5; 95% CI, 1.6 to 80.2).31

Occult malignancy, most commonly lung cancer or lymphoma, has been found in as many as 24% of UEDVT patients.32 The high rate of mortality associated with UEDVT appears to be related more with the patient's overall poor clinical condition rather than directly related to complications from the DVT. However, its presence should alert hospitalists to the patient's potentially poorer prognosis and prompt evaluation for occult malignancy if no risk factor is present.

Back to the Case

This patient should be started on either UFH or LMWH while simultaneously beginning warfarin. She should continue warfarin treatment for at least three months, with a goal INR of 2.0 to 3.0, similar to treatment for LEDVT. The ultimate treatment duration with warfarin follows the same guidelines as treatment with a LEDVT. Although prophylaxis is not routinely recommended, dosing 1 mg of warfarin beginning three days before subsequent CVC placement should be considered if this patient requires a future CVC. Additionally, an evaluation for occult malignancy should be considered in this patient.

Bottom Line

Upper extremity DVT is not a benign condition, and is associated with a general increase in mortality. It should be treated similarly to LEDVT in order to decrease PTS, recurrent DVT, and PE. TH

Dr. Hollberg is a clinical instructor in the section of hospital medicine at Emory University Hospital in Atlanta.

References

  1. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. A statement for healthcare professionals. Council on Thrombosis, American Heart Association. Circulation. 1996;93(12):2212-2245.
  2. Gerotziafas GT, Samama MM. Prophylaxis of venous thromboembolism in medical patients. Curr Opin Pulm Med. 2004;10(5):356-365.
  3. Kabani L, et al. Upper extremity DVT as prevalent as lower extremity DVT in ICU patients. Society of Critical Care Medicine (SCCM) 38th annual Critical Care Congress: Abstract 305. Presented Feb. 2, 2009.
  4. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(6Suppl):454S-545S.
  5. Joffe HV, Kucher N, Tapson VF, Goldhaber SZ. Upper extremity deep vein thrombosis: a prospective registry of 592 patients. Circulation. 2004;110:1605.
  6. Munoz FJ, Mismetti P, Poggio R, et al. Clinical outcome of patients with an upper-extremity deep vein thrombosis: results from the RIETE registry. Chest. 2008,133:143-148.
  7. Coon WW, Willis PW. Thrombosis of axillary and subclavian veins. Arch Surg. 1967;94(5):657-663.
  8. Horattas MC, Wright DJ, Fenton AH, et al. Changing concepts of deep venous thrombosis of the upper extremity—a report of a series and review of the literature. Surgery. 1988;104(3):561-567.
  9. Bernardi E, Piccioli A, Marchiori A, Girolami B, Prandoni P. Upper extremity deep vein thrombosis: risk factors, diagnosis, and management. Semin Vasc Med. 2001;1(1):105;110.
  10. Heron E, Lozinguez O, Alhenc-Gelas M, Emmerich J, Flessinger JN. Hypercoagulable states in primary upper-extremity deep vein thrombosis. Arch Intern Med. 2000;160:382-386.
  11. Ninet J, Demolombe-Rague S, Bureau Du Colombier P, Coppere B. Les thromboses veineuses profondes des members superieurs. Sang Thromb Vaisseaux. 1994;6:103-114.
  12. Painter TD, Kerpf M. Deep venous thrombosis of the upper extremity five years experience at a university hospital. Angiology. 1984;35(35):743-749.
  13. Chan WS, Ginsberg JS. A review of upper extremity deep vein thrombosis in pregnancy: unmasking the “ART” behind the clot. J Thromb Haemost. 2006;4(8):1673-1677.
  14. Hughes MJ, D’Agostino JC. Upper extremity deep vein thrombosis: a case report and review of current diagnostic/therapeutic modalities. Am J Emerg Med. 1994;12(6):631-635.
  15. Prandoni P, Polistena P, Bernardi E, et al. Upper extremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med. 1997;157:57-62.
  16. Van Rooden CJ, Tesslar ME, Osanto S, Rosendal FR, Huisman MV. Deep vein thrombosis associated with central venous catheters—a review. J Thromb Haemost. 2005;3:2049-2419.
  17. Horattas MC, Wright DJ, Fenton AH, et al. Changing concepts of deep venous thrombosis of the upper extremity—report of a series and review of the literature. Surgery. 1988;104(3):561-567.
  18. Bernardi E, Pesavento R, Prandoni P. Upper extremity deep venous thrombosis. Semin Thromb Hemost. 2006;32(7):729-736.
  19. Baxter GM, McKechnie S, Duffy P. Colour Doppler ultrasound in deep venous thrombosis: a comparison with venography. Clin Radiol. 1990;42(1):32-36.
  20. Bern MM, Lokich JJ, Wallach SR, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med. 1990;112(6):423-428.
  21. Couban S, Goodyear M, Burnell M, et al. Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer. J Clin Oncol. 2005;23(18):4063-4069.
  22. Lokich JJ, Both A, Benotti P. Complications and management of implanted central venous catheters. J Clin Oncol. 1985;3:710-717.
  23. Moss JF, Wagman LD, Rijhmaki DU, Terz JJ. Central venous thrombosis related to the silastic Hickman-Broviac catheter in an oncologic population. J Parenter Enteral Nutr. 1989;13:397.
  24. Machleder HI. Evaluation of a new treatment strategy for Paget-Schroetter syndrome: spontaneous thrombosis of the axillary-subclavian vein. J Vasc Surg. 1993;17:305-315.
  25. Malcynski J, O’Donnell TF, Mackey WC. Long-term results of treatment for axillary subclavian vein thrombosis. Can J Surg. 1993;36:365-371.
  26. Elman EE, Kahn SR. The post-thrombotic syndrome after upper extremity deep vein thrombosis in adults: a systematic review. Thromb Res. 2006;117(6):609-614.
  27. Baarslag HJ, Koopman MM, Hutten BA, et al. Long-term follow up of patients with suspected deep vein thrombosis of the upper extremity: survival, risk factors and post-thrombotic syndrome. Eur J Intern Med. 2004;15:503-507.
  28. Prandoni P, Bernardi E, Marchiori A, et al. The long term clinical consequence of acute deep venous thrombosis of the arm: prospective cohort study. BMJ. 2004;329:484-485.
  29. Monreal M, Raventos A, Lerma R, et al. Pulmonary embolism in patients with upper extremity DVT associated to venous central lines—a prospective study. Thromb Haemost. 1994;72(4):548-550.
  30. Hingorani A, Ascher E, Lorenson E, et al. Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population. J Vasc Surg. 1997;26:853-860.
  31. Blom JW, Doggen CM, Osanto S, Rosendaal FR. Old and new risk factors for upper extremity deep vein thrombosis. J Thromb Haemost. 2005;3:2471-2478.
  32. Girolami A, Prandoni P, Zanon E, Bagatella P, Girolami B. Venous thromboses of upper limbs are more frequently associated with occult cancer as compared with those of lower limbs. Blood Coagul Fibrinolysis. 1999;10(8):455-457.

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