Upper-extremity deep vein thrombosis. (Featured CME Topic: Upper-Extremity DVT).

Abstract: Upper-extremity deep vein thrombosis (UED VT) was an understudied disease until recently. Previously thought of as benign, UEDVT has been shown in recent studies to pose a significant risk for pulmonary embolus and death. This article reviews the epidemiology, risk factors, clinical features, diagnostic tests, treatment options, complications, and prevention strategies for patients with UED VT.

Key Words: deep vein thrombosis, treatment, upper extremity

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Upper-extremity deep vein thrombosis (IJEDVT) is understudied, even though it may account for as many as 4% of all cases of deep vein thrombosis (DVT). (1) First described separately by Paget (2) and Von Schroetter (3) in the late 1 800s, the incidence of UEDVT has increased during the past 2 decades. This increase is thought to be secondary to awareness among health care professionals, better methods of detection, and increasing use of indwelling central upperextremity catheters. (2-5) The true incidence of the disease may be underrepresented, however, because UEDVT is most often asymptomatic. As has been well established for lower-extremity DVT (LEDVT), UEDVT is important because it can cause significant morbidity and mortality. Initially thought to be benign, recent studies have shown that UEDVT may lead to a greater number of pulmonary emboli than previously recognized. (6)

Classification and Risk Factors

UEDVT is classified into two types: primary and secondary. Primary UEDVT is either "idiopathic" or "effortrelated" and accounts for approximately 20% of all cases of UEDVT. (7) Effort-related UEDVT is also known as PagetSchroetter disease. This disease generally affects young, healthy, active males after strenuous exercise and may be related to anatomic abnormalities such as a cervical rib.8 In most cases, a predisposing factor is not discovered.

Secondary UEDVT accounts for the majority of UEDVT cases. These cases are thought to be a result of some identifiable risk factor, as generally outlined by Virchow. As Virchow described, these cases of DVT are usually the result of perturbations in the coagulation state or disruption of the blood vessel or blood flow, resulting in stasis. Common causes of secondary UEDVT therefore include central indwelling venous catheters, hypercoagulable states, malignancy, previous surgery, and infection. (6,8,9) Table 1 summarizes the causes of secondary UEDVT.

Catheter-related UEDVT may be present in as many as 72% of cases of catheter placement. (10) Numerous factors regarding catheters have been studied that may lead to the formation of UEDVT. The circumference of the catheter may lead to a mechanical disruption of the intima of the vessel and thus to UEDVT. Some studies have shown that large catheters result in a higher incidence of UEDVT. (1) The length of time that the catheter is left in place and the type of catheter used are thought to be important variables. The longer a catheter remains in the patient, the more likely it is that UEDVT will develop. (11-13) Silicone catheters have been shown to be less likely than polyvinyl chloride-coated catheters to cause UEDVT. (11,13) Also, the characteristics of the infusate delivered through the catheter may play a role in the development of an UEDVT, with pH, osmolarity, and amino acids being important contributing factors. (14) These entities are thought to vary in their irritation of the vessel and thus in the d egree to which they initiate the coagulation process.

Although the presence of a primary hypercoagulable state has received some attention, the association of hypercoagulability with the presence of UEDVT remains controversial. The correlation of UEDVT to hypercoagulable state has been estimated to range from 8 to 61%. Hypercoagulable states have been associated with primary UEDVT. These coagulation disorders include anticardiolipin antibodies, factor V Leiden, protein S deficiency, antithrombin III disorder, and protein C deficiency. (5,15,16)

Epidemiology

One study suggested that UEDVT accounted for less than 2% of all DVT between 1966 and l986. (17) These data were retrospective, however, and were not based on a review of all of the upper extremities among patients at risk for DVT. Patients with secondary UEDVT are generally older than 50 years of age. (6,10,18,19) There are conflicting reports in the literature with regard to the influence of patient sex. Some studies indicate a female predominance, whereas others show a male predominance and still others demonstrate an equal distribution between men and women. (16,10,18,20) The site of thrombus formation in UEDVT is most often the subclavian vein (18-69%), followed by the axillary (5-42%), internal jugular (8-29%), and brachial (4-13%) veins. (6,10,18) Often multiple veins are involved, but bilateral UEDVT is rare (less than 6%). (5,6,18) The side of disease has been studied and remains controversial. Some studies indicated a left-sided predominance, whereas others show right-sided predominance, and still o thers demonstrate an equal incidence on the left and right sides. (1,6,10,21) In catheter-related UEDVT, the correlation of the side of catheter placement with UEDVT incidence is well documented. (10,14)

Clinical Features

Patients with UEDVT generally present within the first 2 to 3 days of symptom onset. As is the case with LEDVT, most cases of UEDVT are thought to be asymptomatic. Among patients who do present with symptoms, pain is the most common symptom, occurring in 63% of the cases. (4) This pain has been characterized as a dull ache, localized tenderness, and/or constant disabling pain. (6) Other symptoms include numbness, heaviness, paresthesias, pruritus, and coldness of the affected extremity. (4,6,8,21) Physical signs, when present, are helpful clues to the diagnosis of an UEDVT. Edema, the most common physical sign, occurs in 98% of cases. (4) Other signs include discoloration, erythema, distended collateral veins at the shoulder girdle, tendemess, limitation in range of motion, and warmth of the affected extremity. (4) The signs and symptoms of UEDVT are nonspecific. The differential diagnosis includes superficial venous thrombophlebitis, lymphedema, neoplastic compression leading to outlet obstruction, hematoma, contusion, muscle tears, occult fracture, heterotopic ossification, and chronic regional pain syndrome type 1. (6,22,23) As with LEDVT, the clinical examination findings are extremely unreliable for diagnosing UEDVT. The prevalence of disease is less than 50% in symptomatic patients. (6) Therefore, objective testing is needed for confirmation before beginning treatment. (24)

Diagnosis

Diagnostic testing is divided into two categories: noninvasive and invasive. Noninvasive testing is used most often. Impedance plethysmography, strain gauge plethysmography, thermography, and phleborheography have been used; however, they lack sensitivity and specificity. (25-28) Most often ultrasonographic testing is used for diagnosis, because it can be performed at the bedside. Currently, the most commonly used ultrasonographic method is real-time B-mode ultrasonography with venous compression. This method has been shown to have sensitivity as high as 96% and specificity as high as 94% in detecting UEDVT, although data reported in lower-extremity studies suggest that this may be a gross over-estimation among patients without symptoms or signs. Other ultrasonographic methods that are useful in detecting UEDVT are duplex and color Doppler. Continuous wave Doppler is thought to be less accurate. (6) The main disadvantages of ultrasonographic methods are a blind spot caused by the shadow formed by the clavicle , that they are operator-dependent, and that the studies produced can be more difficult to interpret if there are a large number of collaterals, thereby increasing the false-negative rate. (29,30) In selected cases, magnetic resonance imaging and spiral computed tomography may be helpful, noninvasive diagnostic modalities. (8) Contrast venography is the invasive method of choice and the "gold standard" for diagnosis. Contrast venography allows for direct visualization of the clot and can allow the identification of the extent of the clot and collaterals; however, it is invasive, painful, requires potentially allergenic contrast, and is technically difficult. It also may worsen or cause the recurrence of UED VT. (31)

Complications

Historically, UEDVT was thought to be a benign disease that does not lead to significant morbidity or mortality. Recent studies have shown significant complications of UED VT, including pulmonary embolism and postthrombotic syndrome. (6) The complication of DVT that is of most concern is progression to pulmonary embolism (PE). Although PE has been thought to be a rare complication of UEDVT, recent data suggest that it may be present in as many as 36% of cases of UEDVT. (6) As has been shown in the LEDVT literature, the prospective studies that review both symptomatic and asymptomatic patients reveal a larger number of UEDVT cases than do studies that use a retrospective review of patients with those symptoms. (19) Also, PE is found more often in catheter-related UEDVT and is twice as likely to be seen in connection with secondary UEDVT than with primary UEDVT. (8, 19) One study found a higher mortality rate and greater incidence of PE when UEDVT cases were compared with LEDVT cases. (18)

Another important complication is the postthrombotic syndrome. Venous hypertension, arm swelling, pain, paresthesias, and functional limitations characterize this syndrome. The incidence of this syndrome among patients with UEDVT has been reported to be as high as 90%. (16,22,32) The incidence of postthrombotic syndrome may be related to the timing and the mode of treatment of UEDVT. Data suggest that thrombolysis may result in fewer cases of postthrombotic syndrome than traditional treatments of heat and elevation or IV heparin. Thrombolysis is thought to be the only treatment that causes an actual decrease in the size of the clot. There have been cases of LEDVT in which the size of the clot was reduced through the use of low molecular weight heparin, but this effect has not yet been shown in patients with UEDVT. Prompt treatment may afford a better chance of avoiding postthrombotic symptoms. (20)

Treatment

Treatment of UEDVT is controversial. Historically, treatment was supportive, alleviating symptoms by elevation of the affected extremity and administration analgesia and warm compresses to the affected extremity. Other treatment options focus on targeting the cause of UEDVT. Surgical interventions include thrombectomy and catheter-directed balloon angioplasty and stenting. (25,31,33) Another treatment option that has been used with success is either systemic or local thrombolysis with a thrombolytic agent. (32)

The current standard treatment is anticoagulation with either IV unfractionated heparin or subcutaneous injections of a low molecular weight heparin followed by 3 months or more of warfarin. (5,8,34) This may reduce or prevent the complications of PE and postthrombotic syndrome. These interventions may also prevent clot propagation and facilitate the maintenance of venous collaterals. (31,34,35) However, there are no controlled studies demonstrating the optimal anticoagulant agent and duration of treatment for this condition. In patients in whom anticoagulation has failed or for whom it is contraindicated, a superior vena cava filter may be an alternative option for preventing PE. (36,37)

Prevention

It is generally recognized that only a small minority of all UEDVTs are actually symptomatic. Physical examination techniques as screening tools for patients who are at risk but are asymptomatic are virtually futile. Because screening with the use of ultrasonography can be expensive and time-consuming, it is thought that prophylaxis is the only reasonable way to proceed in attempting to prevent UEDVT among those at risk. DVT preventive measures should be considered in all patients at risk for the development of DVT. The use of both pharmacologic and nonpharmacologic methods for LEDVT prevention has been well documented. (38) There is little evidence regarding methods for the prevention of UEDVT, however. One study in which 1 mgld warfarin was used in patients with neoplasms and an indwelling venous catheter found a reduction in the incidence of UEDVT. (18) Another study found similar results but used low molecular weight heparmn every day for 90 days. (39) Data concerning the prevention of UEDVT is far less e xtensive than that for LEDVT prevention.

Conclusions

Literature concerning the incidence of UEDVT has increased during the past few decades. During that same period, there has been a good deal of research concerning the incidence and the need to prevent LEDVT. The literature exploring the dangers of the UEDVT has yet to meet the level of that surrounding LEDVT. The existing data for UEDVT do demonstrate that UEDVT poses a serious risk for catastrophic events. As clinicians begin to appreciate this fact, they must be aware of the risk and realize the need to screen for UEDVT among patients at risk. Although the literature has not progressed such that the relative risks of UEDVT and LED VT can be quantified in any individual patient, the data described in this review indicate a need for broader vigilance in the search for potential locations of catastrophic pulmonary emboli.

Table 1

Risk factors for secondary upper-extremity deep vein thrombosis (a)

Risk factor                           Risk level

Central indwelling catheter           29-72%
Nonmalignancy-related coagulopathies  10-61%
Malignancy                            22-37%
Infection                             21-28%
Previous surgery                      12-21%
Renal failure                         21%
Immobility                            21%
History of LEDVT                      8-18%
Concurrent LEDVT                      13%
Cardiopathy                           8-13%
Trauma                                9%
Pacemaker                             4-8%
Stroke                                7%
Vasculitis                            6%
Medications                           4%

(a) LEDVT, lower-extremity deep vein thrombosis.

Sources: Burihan E, de Figueiredo LF, Francisco J Jr. Miranda F Jr.
Upper-extremity deep venous thrombosis: Analysis of 52 cases. Cardiovasc
Surg 1993:1:9-22; (4) Hingoran A, Ascher E, Yorkovich W, Mazariol F,
Jacob T, Gunduz Y, et al. Upper extremity deep venous thrombosis: An
underrecognized manifestation of a hypercoagulable staet. Ann Vasc Surg
2000;14:421-426; (5) Marinella MA, Kathula SK, Market RJ. Spectrum of
upper-extremity deep venous thrombosis in a community teaching hospital.
Heart Lung 2000;29:113-117; (10) Hingorani A, Ascher E, Hanson J,
Scheinman M, Yorkovich W, Lorenson E, et al. Upper extremity versus
lower extrekity deep venous thrombosis. Am J Surg 1997;174:214-217. (18)

Accepted February 3, 2003.

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RELATED ARTICLE: Key Points

* Upper-extremity deep vein thrombosis is an understudied condition with serious consequences such as pulmonary embolus if left untreated.

* Indwelling catheters are a major source of upper-extremity deep vein thrombosis.

* Upper-extremity deep vein thrombosis needs to be treated with anticoagulation therapy.

From the Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital/Harvard Medical School, and the Department of Medicine, Massachusetts General Hospital, Boston, MA.

We received no financial support and do not have a commercial or proprietary interest in any drug, device, or equipment mentioned in this article.

Reprint requests to Mrugeshkumar K. Shah, MD, MPH, MS, 10 Summer Street, Suite 303S, Malden, MA 02148. Email: [e-mail]

Copyright [C] 2003 by The Southern Medical Association

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