Upper Extremity Venous Thrombosis
Michael T. Caps
Bridget A. Mraz
In most vascular laboratories, the upper extremity venous duplex examination is performed less frequently than is the lower extremity venous examination. Whereas the basic principles of duplex scanning of the lower extremity venous system also apply to the upper extremity venous system, there are important differences between lower and upper extremity veins with respect to physiology, anatomy, and pathophysiology. An understanding of these differences is a prerequisite for the performance of a proper upper extremity venous duplex evaluation.
There are two major physiologic differences between upper and lower extremity venous flow. First, there is a marked difference in the phasicity of flow related to the respiratory cycle: In the lower extremity veins, flow decreases during inspiration and increases during expiration, whereas in the upper extremity, venous flow has the opposite relationship with respiration. This difference is caused by the interposition of the abdomen between the thorax and the lower extremities. During inspiration, intrathoracic pressure drops, causing an increase in the upper extremity venous pressure gradient and a consequent increase in venous flow from the upper extremities into the chest. However, inspiration is accompanied by descent of the diaphragm with a resulting increase in intra-abdominal pressure. Because veins are collapsible tubes, this increase in intraabdominal pressure impedes venous outflow from the legs.
A second important physiologic difference between lower and upper extremity venous flow is an often pronounced increase in pulsatility in the upper extremity venous flow pattern, particularly in the more central, axillosubclavian venous segment. This is due to the proximity of the upper extremity veins to the heart. The abdominal venous segments serve as a buffer that dampens out the central venous pressure changes and makes them less detectable in the femoral veins. This increased pulsatility in the upper extremity veins can be particularly marked in patients with elevated right heart pressures due to heart failure, pulmonary hypertension, and tricuspid stenosis or regurgitation. Conversely, pulsatility in these veins may be blunted by the presence of more central venous occlusion.
An important anatomic difference between the upper and lower extremity veins is that a significant portion of the axillosubclavian venous segment lies within the bony thorax or within the thoracic outlet, which can render these veins difficult to image and difficult to compress with the ultrasound probe. As is discussed later in this chapter, these difficulties can often be overcome with the use of small ultrasound probes and color-flow and Doppler spectral waveforms.
A key difference in the pathophysiology of the upper and lower extremity veins is the mechanism by which pathologic conditions in these veins lead to disease states. Deep vein thrombosis (DVT) of the lower extremity is more likely to be associated with clinically significant pulmonary embolism (PE) and limb-threatening venous hypertension (phlegmasia cerulea dolens, venous gangrene) than is upper extremity DVT. Whereas thrombosis of the femoral, popliteal, and calf veins is common and frequently leads to severe symptoms in the lower extremity, analogous thrombosis of the brachial and deep forearm veins (in the absence of axillosubclavian thrombosis) is relatively uncommon and is less often associated with severe clinical symptoms.
Because of their dependent position and longer length, flow in the lower extremity veins is more affected by gravity than is flow in the upper extremity veins. Consequently, venous function in the legs relies more upon the presence of intact and competent venous valves. Although obstruction and incompetence both play important roles in the development of symptoms related to the lower extremity veins, the chronic and often debilitating symptoms of stasis dermatitis and ulceration are more frequently caused by reflux due to venous valvular incompetence. In contrast, these postthrombotic sequelae are less frequently seen in the upper extremity where obstruction (and particularly central venous obstruction) is the predominant pathophysiologic feature.
This chapter describes the technique for performing an upper extremity venous duplex examination for venous thrombosis. In order to provide a clinical context for this application of duplex scanning, the presentation, diagnosis, and treatment of upper extremity venous thrombosis is covered first. This discussion focuses mainly on axillosubclavian venous thrombosis, but jugular, brachial, and forearm DVT, as well as superficial thrombophlebitis of the cephalic and basilic veins, are also mentioned. The related topic of duplex
scanning in the evaluation of dialysis access procedures is covered in Chapter 33. Preoperative vein mapping is discussed in Chapter 28.
scanning in the evaluation of dialysis access procedures is covered in Chapter 33. Preoperative vein mapping is discussed in Chapter 28.
BRACHIOCEPHALIC VENOUS THROMBOSIS
Etiology
Approximately 5% to 10% of all cases of DVT involve the upper extremity veins.1,2,3,4 Upper extremity DVT is classically divided into two major types: primary and secondary. Thrombosis in both primary and secondary cases of upper extremity DVT usually occurs in the presence of one or more elements of Virchow’s triad: endothelial damage, stasis, and hypercoagulability (Fig. 20.1).
First described by Paget and von Schrötter in the late 1800s and subsequently named the “Paget-Schrötter syndrome,” a significant fraction of cases of primary upper extremity DVT are caused by compression of the axillosubclavian venous segment at the thoracic outlet, usually in the vicinity of the first rib. This is commonly referred to as “venous thoracic outlet syndrome.” It is hypothesized that thrombosis is preceded by many years of intermittent compression and repetitive trauma to this venous segment, accompanied by the accumulation of scar tissue. In these patients, compression of the subclavian vein can be induced during the performance of upper extremity venography by several provocative body positions, including hyperabduction and external rotation of the shoulder, extension of the neck, and caudal and posterior movement of the shoulder.5 However, the situation is complicated by the fact that many asymptomatic individuals will also demonstrate these changes on provocative venography. Additionally, a minority of patients with primary upper extremity DVT, many of whom have hypercoagulable states, have no evidence of thoracic outlet compression even with provocative arm and shoulder positioning.
Approximately 75% of upper extremity DVT cases are termed “secondary” DVT, the majority of which are caused by the presence of indwelling medical devices such as central venous catheters and pacemaker wires.2,6 In addition, the presence of known or occult malignancies, with or without an indwelling catheter, is an important factor in the pathogenesis of secondary upper extremity DVT.7 In hospital settings, secondary DVT, particularly those cases associated with indwelling catheters and pacemakers, is far more common than is primary upper extremity DVT.
 FIGURE 20.1. Virchow’s triad of thrombus formation. |
Diagnosis
The majority of patients presenting with the Paget-Schrötter syndrome (also called “effort thrombosis”) are young, athletic, and often muscular males, although the condition is certainly not limited to this demographic group. The clinical hallmark of the Paget-Schrötter syndrome is ipsilateral upper extremity swelling that typically involves the upper arm, forearm, and hand and is predominantly nonpitting, particularly during the acute phase. Pain is also a frequent symptom, usually described as “tightness” or “heaviness,” and is often exacerbated by dependency and partially ameliorated by elevation. Because these patients have venous hypertension in the affected extremity, the veins of the arm and hand are often distended, although this may not be readily apparent because the venous distention is often masked by edema. Although not necessarily present in the acute phase, enlarged venous collaterals are usually visible around the shoulder.
The clinical presentation of patients with catheter-associated upper extremity DVT can be more subtle than the presentation of Paget-Schrötter syndrome.8 Thrombus associated with indwelling catheters often develops more slowly (allowing more time for the development of venous collaterals) and typically involves a shorter venous segment than primary DVT. Furthermore, the affected patients usually have multiple medical comorbidities (e.g., cancer, heart failure, end-stage renal disease) rendering them far more sedentary than the typical patient with Paget-Schrötter syndrome.
Prior to obtaining objective diagnostic tests, it is possible to stratify patients according to low, intermediate, and high pretest probability for upper extremity DVT in much the same way as has been demonstrated for lower extremity DVT. Constans et al9 used logistic regression on a derivation sample of 140 patients. These authors developed a clinical scoring system in which a point is added for the presence or absence of swelling, pain, and an indwelling catheter or pacemaker, and a point is subtracted when there is a plausible alternative diagnosis. The scoring system was then tested in a 214 patient validation sample. Among patients with a score of -1 or 0 (low probability), 1 (intermediate probability), and 2 or 3 (high probability), upper extremity DVT was found in 13%, 38%, and 69% of patients, respectively.
Because of its low specificity, a positive D-dimer test cannot be used to diagnose upper extremity DVT. A negative D-dimer result can be used to confidently rule out DVT, particularly among patients with a low pretest probability of upper extremity DVT. However, the clinical usefulness of this approach is limited by the fact that the majority of patients with suspected upper extremity DVT who have cancer or indwelling catheters or pacemakers will also have elevated D-dimer results.10
The most commonly employed diagnostic imaging tests are duplex ultrasonography and catheter venography, although magnetic resonance venography (MRV) and computed tomography venography (CTV) may also play important roles depending on local expertise and availability. Although studies of MRV show particularly promising results when performed in centers of excellence, this discussion focuses on duplex scanning because it is far more commonly used in clinical practice, is less costly, and does not involve the use of contrast agents that can pose risks to the patient.
Table 20.1 summarizes the studies in which the accuracy of duplex scanning for the diagnosis of upper extremity DVT has been quantified using catheter contrast venography as the reference or “gold standard.”6,11,12,13,14,15,16 However, it should be emphasized that venography is not a perfect standard in this setting. When two “blinded” radiologists interpret the same venogram, there is considerable disagreement.17 In addition, there are cases of nonocclusive upper extremity DVT
diagnosed by duplex scanning in which the venogram is interpreted as being “normal,” and venography is clearly inferior to duplex scanning in detecting jugular venous thrombosis. These caveats aside, a well-performed venogram is, in most clinical settings, the final arbiter for the presence or absence of upper extremity DVT.
diagnosed by duplex scanning in which the venogram is interpreted as being “normal,” and venography is clearly inferior to duplex scanning in detecting jugular venous thrombosis. These caveats aside, a well-performed venogram is, in most clinical settings, the final arbiter for the presence or absence of upper extremity DVT.
TABLE 20.1 SUMMARY OF REPORTED STUDIES IN WHICH THE RESULTS OF DUPLEX SCANNING FOR AXILLARY AND SUBCLAVIAN VENOUS THROMBOSIS WERE VALIDATED USING VENOGRAPHY AS THE “GOLD STANDARD” | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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The accuracy of duplex scanning in diagnosing DVT of the upper extremities has been far less extensively studied than in the lower extremities. The published studies (see Table 20.1) have demonstrated considerable variability in study methodologies, including the proportion of patients with catheter-associated DVT. Taking a weighted average of these studies yields a sensitivity (86%) that is slightly lower than the specificity (90%), but the heterogeneity in reported results is striking, ranging from 56% to 100% for sensitivity and from 82% to 100% for specificity. Some of the variability in results is almost certainly due to the fact that duplex scanning is operator dependent, and this operator dependence is probably more of a factor in the upper extremity venous system owing to the difficulty of imaging underneath the clavicle where most clinically important upper extremity DVT occurs. A list of indications for upper extremity venous duplex scanning is given in Table 20.2.
While upper extremity venous duplex scanning is the most frequently employed imaging test for the diagnosis of DVT in most centers, there is still an important subset of patients who are appropriate for venography. Among patients for whom there is an intermediate or high clinical suspicion of upper extremity DVT, particularly those who would be candidates for catheter-directed thrombolysis, a strong argument can be made for ignoring a negative duplex scan result or omitting the duplex scan altogether and proceeding directly to venography. Conversely, for patients who are not considered candidates for catheter-directed thrombolysis, the decision to anticoagulate is often based solely on the results of the duplex scan. Among patients who are not considered candidates for thrombolysis and who have had a negative duplex scan, but for whom there is still a high clinical suspicion of upper extremity DVT, venography should be considered and MRV or CTV may also be useful. It should be noted that no studies have examined clinical outcomes resulting from withholding treatment on the basis of a negative duplex scan of the upper extremity veins.
TABLE 20.2 INDICATIONS FOR UPPER EXTREMITY VENOUS DUPLEX SCANNING | ||
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Prognosis
Since the majority of patients with upper extremity DVT are treated with anticoagulation, little is known about the natural history of upper extremity DVT without treatment. Clinically important outcomes include mortality, PE, recurrent thrombosis, and alleviation of acute and chronic (“postthrombotic syndrome”) symptoms. In most modern series of upper extremity DVT, mortality rates are substantial owing to the coexistence of cancer, central venous catheters, cardiac disease, pacemakers, and automatic implantable cardiac defibrillators.3,18,19,20 The vast majority of these deaths are due to the patient’s underlying disease rather than to PE. In contrast, patients with Paget-Schrötter syndrome are typically young and healthy with a markedly better prognosis.
As mentioned previously, PE, and particularly symptomatic PE, is less frequently associated with upper extremity DVT than with lower extremity DVT. Explanations for this difference include the smaller size of upper extremity venous thrombi and variations in mechanical forces and flow dynamics. In studies with heterogeneous combinations of primary and secondary DVT and treatment strategies ranging from no anticoagulation to standard anticoagulation with or without thrombolytic therapy, the incidence of reported PE associated with upper extremity DVT has ranged from 0% to 25%.4,21,22,23,24,25,26 Because the majority of emboli associated with DVT of the brachial and cephalic veins are asymptomatic, the frequency of detected PE will depend on how aggressively the diagnosis is sought. In a prospective study of 86 patients with catheter-associated upper extremity DVT, all of whom were anticoagulated and received ventilation-perfusion lung scans, Monreal et al25 found PE in 13 patients (15%); 11 of these patients were asymptomatic, while 2 had symptomatic and fatal PE.
In a comprehensive literature review of patients with primary upper extremity DVT, Thomas and Zierler26 found a reported incidence for PE of 12% among those treated without anticoagulation (rest, heat, and elevation of the effected limb) versus 7% for those who were anticoagulated. Although not known with certainty, the rate of PE is most likely similar among patients with primary versus secondary upper extremity DVT. While the data on jugular vein thrombosis are sparse, the available literature suggests a similar risk of PE compared with that of upper extremity DVT.21,24,27 It is generally believed that isolated DVT occurring distal to the shoulder (i.e., in the brachial or forearm veins), as well as superficial thrombophlebitis involving the cephalic and basilic veins, are both associated with very low risks of PE. However, PE has been reported in both of these subgroups, including one study of 52 patients with isolated brachial vein thrombosis in which the proportion of patients with documented PE was 11.5%.28
The risks of recurrent thrombosis and chronic postthrombotic symptoms are also substantially lower following upper extremity DVT compared with lower extremity DVT. The risk of symptomatic upper extremity recurrent thrombosis is 2% to 5% at 12 months and 5% to 15% at 5 years.3,18,29 The corresponding figures for lower extremity DVT are 5% to 15% at 12 months and 20% to 30% at 5 years.30,31 As previously mentioned, the risk of long-term postthrombotic symptoms is considerably lower in the arm than in the leg. The proportion of patients suffering long-term postthrombotic symptoms following upper extremity DVT is approximately 15% compared to 30% to 60% following lower extremity DVT.31,32,33 Patients who suffer long-term postthrombotic symptoms in the upper extremity are more likely to have residual axillosubclavian vein occlusion and are less likely to have suffered catheter-associated thrombosis.32
Treatment
The goals of treatment for patients with upper extremity DVT are to prolong life, alleviate acute symptoms, and minimize the risk of PE, symptomatic recurrent thrombosis, and the postthrombotic syndrome. The treatment of upper extremity DVT may consist of one or more of the following elements: conservative management (rest, heat, elevation, external compression), anticoagulation, central venous catheter removal, thrombolytic therapy, and surgical decompression of the thoracic outlet with or without open or endovascular venous reconstruction.
Because randomized trials of anticoagulant therapy in patients with upper extremity DVT are lacking, recommendations regarding the choice of anticoagulant and duration of therapy for patients with upper extremity DVT are largely extrapolated from data on the treatment of lower extremity DVT. Consensus guidelines from the American College of Chest Physicians provide detailed recommendations for the treatment of upper extremity DVT.34 Salient points from the most recent 9th edition of this guideline statement are reviewed here.
Unless there are contraindications, patients with acute thrombosis of the subclavian or axillary veins should be anti-coagulated.34 Absolute contraindications to anticoagulation include severe active bleeding, intracranial bleeding, recent brain, eye, or spinal cord surgery, pregnancy, and malignant hypertension. Relative contraindications include recent stroke or major surgery and severe thrombocytopenia. In general, superficial venous thrombophlebitis of the cephalic or basilic veins and isolated DVT involving the brachial or forearm veins do not require anticoagulation. However, there is recent evidence to suggest that patients with superficial venous thrombosis of the lower extremity benefit from treatment with prophylactic dose anticoagulation.35 Although somewhat controversial, anticoagulation should be considered in patients with extensive and proximal superficial thrombophlebitis or brachial vein thrombosis when there is active cancer and/or indwelling catheters.
Anticoagulant therapy is typically started parenterally in the form of intravenous unfractionated heparin (IVUFH) or subcutaneous low molecular weight heparin (LMWH). Data from several randomized controlled trials and meta-analyses suggest that LMWH is superior to IVUFH with lower mortality and lower risk of recurrent thrombosis and major bleeding.19,36 Although less compelling, there is evidence to suggest that fondaparinux is also superior to IVUFH for patients with acute DVT and should be considered to have equivalent efficacy and safety compared with LMWH.34 Because LMWH and fondaparinux have significant renal excretion, they are contraindicated in patients with significant renal impairment (glomerular filtration rate <30 mL/min).
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