Eur Radiol (2004) 14:1263–1274 DOI 10.1007/s00330-004-2252-1
Henk J. Baarslag Maria M. W. Koopman Jim A. Reekers Edwin J. R. van Beek
Received: 3 June 2003 Revised: 18 December 2003 Accepted: 8 January 2004 Published online: 26 February 2004 © Springer-Verlag 2004 H. J. Baarslag (✉) · J. A. Reekers Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands e-mail:
[email protected] Tel.: +31-20-5663329 Fax: +31-20-5669119
VA S C U L A R - I N T E RV E N T I O N A L
Diagnosis and management of deep vein thrombosis of the upper extremity: a review
Abstract Deep vein thrombosis of the upper extremity is an increasing clinical problem due to the use of long-term indwelling catheters for chemotherapy or long-term feeding. The clinical diagnosis is difficult to make, and various imaging modalities have been used for this purpose. The use of (interventional) radiological procedures has been advancing in
recent years. This review describes the clinical background, the imaging modalities that may be employed, treatment options and outcome of patients with upper extremity thrombosis. Keywords Thrombosis · Thoracic inlet · Veins · Diagnostic radiology · Therapy
M. M. W. Koopman Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands E. J. R. van Beek Unit of Academic Radiology, Floor C, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK
Introduction Deep vein thrombosis of the upper extremities (DVTUE) can be divided into primary and secondary thrombosis [1]. Primary thrombosis occurs spontaneously or after unusual effort [2]. Secondary thrombosis includes all other causes, mostly related to venous lines and/or cancer [3, 4]. DVTUE was traditionally regarded as a rare clinical entity. This is still true for primary thrombosis with an incidence of two per 100,000 persons a year [5]. However, in recent years the use of intravenous access lines for indications such as chemotherapy and intravenous feeding has increased. As a result, the incidence of deep vein thrombosis associated with subclavian and jugular lines has increased in parallel. In a prospective study of 145 patients with cancer, the incidence of catheter-related DVTUE was 12% [6]. In a recently published
study, two suspected adult cases per month were seen in a 900-bed teaching hospital, with ten confirmed cases per year [7]. The importance of adequate diagnosis cannot be over-emphasised. Early identification of DVTUE will result in early treatment, thus reducing the risk of pulmonary embolism (PE) and permanent occlusion of venous segments, while normal anatomy may be retained. This latter aspect is especially important in patients who rely on repeated indwelling catheters, such as those who are undergoing repeated courses of chemotherapy or require long-term intravenous feeding. Furthermore, early interventions may play a role in catheter salvage, thus reducing the need for removal of lines and reinsertion of new lines with inherent complication risks. This review article aims to describe the clinical background of DVTUE, the diagnostic modalities that may be employed and the treatment options available.
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Pathogenesis Several risk factors for the development of venous thromboembolic disease have been identified. However, for upper extremity thrombosis only limited data exist in studies with relatively small numbers of patients. Table 1 shows an overview of studies that have described potential factors that were considered as predisposing to upper extremity thrombosis. Primary thrombosis was defined as thrombosis in relation to effort, anatomical abnormalities of the thoracic inlet, or unknown reasons (Paget–Schroetter syndrome). Only few studies assessed these risk factors prospectively. It is interesting to note that primary thrombosis seemed more common in earlier studies. This may be the result of the increasing knowledge of pathophysiology and thrombophilia and better detection of cancer. Furthermore, it is obvious that intravenous access lines become more important during later years, especially in combination with malignancy. In secondary DVTUE, malignancy is a frequently encountered diagnosis. In these patients, intravenous lines are often used for chemotherapy and/or feeding purposes. In recent prospective studies, malignancy was present in more than half of the patients, with or without intravenous lines, with proven thrombosis [7, 12, 14]. Two studies describe the effect of incorrect positioning or location of a (central) venous catheter in relation to thrombosis. Compared to chest subcutaneous port catheters, peripheral catheters could be associated with a significantly higher incidence of thrombosis [19]. Correct positioning of the distal tip of the catheter, in the superior caval vein or at the junction between the right atrium and the superior caval vein, could lower the incidence of DVTUE [6]. However, in this study, the side on which
the catheter was implanted did not influence the catheterrelated deep vein thrombosis rate. Only five studies have systematically evaluated the possible influence of hypercoagulability on the development of upper extremity thrombosis, with varying results: range 15–36% (Table 1) [14–18]. The overall prevalence of hypercoagulable states in patients with thrombosis of the upper extremities was not significantly higher than in control subjects, but was significantly lower than that in patients with deep leg vein thrombosis [15].
Diagnostic tests Several diagnostic modalities have been used for the diagnosis of DVTUE. Some of these modalities, such as impedance plethysmography, light reflection rheography and thermography, have only been described in a few reports and generally have additional value only when combined with colour duplex ultrasonography [20–22]. Furthermore, these modalities have mostly been used for deep leg vein thrombosis and are not available in average medical departments. Plasma D-dimer has been investigated mainly in deep leg vein thrombosis and/or PE [23, 24]. Given the high number of patients with malignancy and/or intravenous lines, it is unlikely that plasma D-dimer will play a clinically important role. A possible role could be foreseen for multidetector contrast-enhanced CT, as it is now feasible to perform high-resolution coronal or sagittal reformation to allow for adequate assessment of the venous anatomy of the upper extremity. This could be combined with the evaluation of PE in patients with upper extremity thrombosis. However, no large studies presently exist.
Table 1 Potential predisposing factors for upper extremity deep vein thrombosis (n number of patients with proven thrombosis, Prosp prospective study, ns not specified) Study
Reference
Year
n
Prosp
Primary (%)
Cancer (%)
Lines (%)a
Hypercoagulability (%)
Tilney et al. Prescott et al. Donayre et al. Lindblad et al. Kerr et al. Monreal et al. Burihan et al. Prandoni et al. Martinelli et al. Ruggeri et al. Heron et al. Leebeek et al. Baarslag et al.
[8] [9] [10] [5] [11] [12] [13] [14] [15] [16] [17] [18] [7]
1970 1979 1986 1988 1990 1991 1993 1997 1997 1997 2000 2001 2002
48 12 41 120 85 30 52 27 36 27 51 41 44
No Yes No No No Yes No Yes Yes Yes Yes Yes Yes
31 42 24 10 10 16 18 11 33 ns 100 24 18
6 17 12 11 31 33 23 22 ns ns 0 10 63
17 0 24 24 69 67 29 30 ns ns 0 41b 14
Not tested Not tested 5 Not tested 9 0 Not tested 36 15 22 31 32 5c
a With or without concomitant malignancy b All patients were treated for haematological c Minority of patients tested
malignancies
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Fig. 1 Normal contrast digital subtraction venogram of the upper extremity veins with physiological narrowing of the left subclavian vein behind the clavicle
Fig. 2 Abnormal contrast digital venogram in a patient following chemotherapy for cancer, demonstrating thrombus in the right subclavian vein
Thus, contrast venography is still the main test for diagnosis of upper extremity thrombosis. More recently, noninvasive techniques have also been evaluated, such as ultrasonography and MR imaging, which will be described in more detail.
Only one study has evaluated the intraobserver and interobserver variability of digital subtraction venography [27]. In this study in 62 patients, two radiologists with different background experience obtained kappa values of only 0.46. After a consensus meeting, the same venograms were read in randomised fashion a second time, which improved the kappa value to 0.71. Although these values are probably acceptable, it does raise some doubt over the reliability of the reference standard. However, one has to bear in mind that this study only used the static images obtained, and dynamic and cinematic series were not available at the time of review. It is virtually impossible to define sensitivity and specificity for a reference standard. We are not aware of previous studies where patients with normal venographic findings were systematically followed up while anticoagulants were withheld.
Contrast venography Contrast venography is the standard reference for the diagnosis of upper extremity thrombosis (Figs. 1, 2). It is performed using approximately 20 ml iodinated contrast in a concentration of 240–300 mg I/ml. Ideally, injections should be made into the medial antecubital vein or more distally (in the back of the hand for instance). This will guarantee adequate opacification of the brachial, axillary and subclavian veins. Although power injectors can be used, one would have to perform preliminary pressure measurements to reduce the risk of serious contrast extravasation. Thus hand-injected procedures are more commonly employed. A possible pitfall is non-filling of the cephalic segment and isolated thrombosis of this venous segment could go unnoticed. Furthermore, it is important to perform one series of the superior vena cava during a single breath-hold. Contrast venography may not be feasible in up to 20% of patients due to the inaccessibility of arm veins and contraindications for contrast agents, such as renal failure and hypersensitivity [7, 25, 26].
Duplex ultrasonography Ultrasonography has largely replaced venography in the management of leg vein thrombosis. It is non-invasive, does not require nephrotoxic contrast agents, and is without ionising radiation. Furthermore, it can be performed at the bed-side and is widely available. This would make it an ideal method for the diagnosis of upper extremity
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Fig. 3 a Grey-scale ultrasound image showing iso-echogenic densities in the non-compressible left subclavian vein, compatible with acute thrombosis. b Corresponding contrast digital venogram showing an occlusion in the subclavian vein (thrombosis) with filling of the superior caval vein via extensive collaterals
thrombosis, and several studies have been published on its diagnostic accuracy [7, 14, 28–32]. The technique most commonly employed uses a combination of real-time compression grey-scale ultrasonography, colour Doppler sonography and flow measurements (Duplex technique) with a 7.5-MHz linear-array probe. The definition of thrombosis is a crucial issue. It is widely accepted that non-compressibility of a venous segment with or without visible thrombus constitutes thrombosis (Fig. 3) [7, 14, 33]. However, there is discussion regarding isolated flow abnormalities (Fig. 4), which is of particular importance as the entire venous system of the upper extremity cannot be followed beyond the clavicle [7, 14]. In our opinion, a visible thrombus or non-compressibility of a visible upper extremity vein is diagnostic for the presence of deep vein thrombosis, whereas flow abnormalities alone are only suggestive of thrombosis, i.e. contrast venography has to be done to prove or exclude thrombosis [7]. Several manoeuvres have been suggested to aid the diagnostic process, such as the Valsalva manoeuvre and sniff test [29]. In normal circumstances, the Valsalva manoeuvre will result in a widening of the veins and a reduction of flow due to increased intrathoracic pressure by obstructed expiration. The sniff test will normally give a slight narrowing and enhanced flow by short increased inspiration (sniffing). A major advantage of ultrasonography is that the jugular vein, distal subclavian vein, axillary vein and the upper arm veins are easily visualised, but a drawback is the lack of visualisation of the proximal subclavian vein, the innominate and superior caval vein beyond the clavicle and sternum. Furthermore, ultrasonography can detect other pathology, such as tumour or lymphadenopathy, by direct visualisation.
There are a limited number of published reports on the sensitivity and specificity of ultrasonography in comparison with contrast venography [7, 14, 28, 30, 31, 34]. The reported sensitivity and specificity rates vary from 78 to 100% and 82 to 100%, respectively (Table 2). No studies have specifically addressed interobserver and intraobserver variability, but it is a widely known fact that ultrasonography is operator dependent in daily practice and that some patients may be more difficult to investigate, such as those with very extensive oedema or obesity. CT venography At present, CT venography does not play a role in the routine work-up of suspected DVTUE. The use of radiation and iodinated contrast agents and the relatively high costs compared to ultrasonography are the main reasons for this. However, because of the recent use of multidetector CT equipment where coronal and sagittal slice reformation and 3D reconstruction are possible, it might play a more significant role in the assessment of DVTUE (Fig. 5) [35, 36]. In addition, the possible presence of pulmonary emboli and a possible cause for the arm complaints, besides the thrombosis, can be assessed in the same session. However, the presence of extensive upper extremity thrombosis and small collateral veins can lead to problems when using an automatic contrast injector via the ipsilateral (affected) arm. Thus, preliminary testing has to be done to prevent the risk of contrast extravasation. Simultaneous contrast injection via the contralateral (not affected) arm allows for adequate assessment of the superior caval vein and pulmonary arteries. A recent
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Fig. 4 a Duplex colour ultrasonography demonstration of normal flow pattern in the right subclavian vein near the junction with the jugular vein. b Colour ultrasonography showing partial thrombus in the left axillary vein. c Duplex ultrasonography with slow abnormal flow pattern in the left axillary vein. Differentiation of ob-
struction, compression or thrombus in the proximal veins is not possible and contrast venography should be performed. d Duplex ultrasonography with abnormal flow pattern in a large collateral, which can be misinterpreted for a normal anatomical vein
Table 2 Performance characteristics of previous consecutive duplex colour ultrasonography studies (author, first author of publication, year year of publication, n number of patients) Author
Year
Reference
Sensitivity (%)
Falk
1987
[20]
100
Knudson
1990
[30]
Baxter Kőksoy Prandoni Baarslag
1991 1995 1997 2002
[34] [31] [14] [7]
Specificity (%)
n
Comments
92
22
78
92
91
100 94 100 82
100 88 93 82
19 44 58 99
Small number of patients, normal volunteers included Reference standard: venography, CT and MRI Small number of patients All patients catheter-related thrombosis Relatively small number of malignancies
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study of 18 consecutive patients showed a good correlation of CT venography with digital subtraction venography [37]. Larger prospective comparative studies have to be undertaken to carefully assess the possible role of CT in the diagnostic work-up of patients suspected of having DVTUE. Magnetic resonance imaging
Fig. 5 a Transverse CT image showing thrombus and collaterals in the right subclavian vein. b 3D reconstructive CT image in the same patient seen from above
Magnetic resonance imaging (MRI) has been proven to be increasingly useful for the assessment of vascular abnormalities. MR angiography is now routinely employed in most body areas, while the technique is also under development for more difficult areas such as the pulmonary arteries [38]. MR venography can be performed using non-contrast methods, such as time-of-flight (TOF) or phase-contrast sequences (Fig. 6). However, this technique has not been systematically investigated in patients with suspected upper extremity thrombosis. The use of 2D TOF MR venography has only been evaluated in the use of preoperative planning of access fistula for haemodialysis, but not for assessment of central upper extremity veins [39]. There are two approaches for contrast-enhanced MR venography. Indirect 3D contrast-enhanced MR venography requires an injection with gadolinium-based contrast agents into a dorsal hand vein or into the cubital vein. A single bolus injection of up to 20 ml of gadolinium-DTPA followed by a saline flush is administered by hand. The subtraction method is most commonly used, which requires an initial series to obtain a mask, followed by two or three subsequent series. Data acquisition in the order of 1 s per series can be performed, yielding a dynamic
Fig. 6 a Normal anatomy of the proximal upper extremity veins using 2D time-of-flight MR venography. b Same patient with normal anatomy using gadolinium-enhanced 3D MR venography. c Normal contrast digital venogram in the same patient
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(cinematic) MR venogram [40]. For a direct approach, diluted (1:10–20) paramagnetic contrast medium is continuously injected upstream. This technique requires less contrast and should result in superior contrast-to-noise ratio [41]. The inherent advantages of MR venography are the use of non-nephrotoxic contrast agents and the absence of ionising radiation, making it particularly useful for use in children and patients with contraindications for iodinated contrast media. However, availability of MR systems and the need for intravenous access may limit its use in clinical practice. Interpretation of MR venography is similar to that of contrast venography. However, tortuous venous anatomy and flow abnormalities, especially in 2D TOF sequences, can result in MR signal dropout, which should not be confused with thrombus material. Furthermore, spatial misregistration artefacts due to respiratory motion are more critical in indirect contrast-enhanced MRI, while neighbouring structures, such as arteries, can result in signal voids as well. Port-a-cath is likely to cause flow disturbance due to indwelling catheter. The system itself should not cause any artefacts, as it is MR compatible; however, the remnants of metal following multiple use can give field inhomogeneities. Another interesting new MR-based technique is capable of direct clot imaging without the need for intravenous contrast. Direct thrombus imaging is based on the principle that blood signal changes as it clots over time, with the intermediate production of methaemoglobin. Methaemoglobin yields a reduction in T1, giving rise to increased signal in a heavily T1-weighted sequence. The technique is particularly sensitive to recent thrombosis, which could help to differentiate between old and new clots. Initial studies have used this technique for lower extremity thrombosis [42], and one can extrapolate that this sequence will do equally well in the upper extremity.
Treatment options The optimum treatment for upper extremity thrombosis is not known with certainty. Treatment generally has two main goals. The first aim is to halt the propagation of thrombi and reduce the risk of secondary events, such as recurrence of the disease and (fatal or non-fatal) PE. Secondly, treatment aims to allow the recanalisation of thrombus, which should ideally result in preservation of normal anatomy. In general, therapy for primary thrombosis is directed at minimising long-term sequelae of venous insufficiency, often necessitating a complicated and multimodal approach. Patients with secondary thrombosis rapidly become asymptomatic with anticoagulation therapy and with removal of the thrombogenic stimulus, for example, the catheter. The four different treatment options for arm vein thrombosis— anticoagulant therapy, fibrinolytic therapy,
surgery or interventional radiologic techniques—are individually described. Anticoagulant therapy Although the evidence from large clinical trials is lacking, anticoagulant therapy is considered to be the cornerstone of therapy for thrombosis of the upper extremities. Standard anticoagulant therapy traditionally includes a first treatment period with either unfractioned heparin or low-molecular-weight heparin for at least 5–7 days followed by a period of at least 3 months with vitamin K antagonist. Unfortunately, standard therapy is often not capable of achieving recanalisation, thus leading to permanent obstruction of the veins and formation of collaterals. These collaterals are often no longer accessible for placement of intravenous lines. Therefore, more aggressive treatment options such as fibrinolytic or interventional therapies may be needed in some patients. Fibrinolytic therapy Only a few studies have prospectively compared the efficacy and safety of anticoagulant or thrombolytic therapy. The advantages of fibrinolytic therapy are more complete lysis of the thrombi and better restoration of the patency of the veins [43]. It is assumed and has been shown in small studies that patent veins will result in fewer post-thrombotic complaints [44]. The great disadvantage of fibrinolytic therapy is the greater risk of bleeding. In several studies of DVTUE (some in combination with central venous catheters), major and minor bleeding occurred in 0–4% and 0–42% of patients, respectively [44–46]. This excess risk of bleeding may be overcome by the use of catheter-directed thrombolysis. Unfortunately, no controlled trials or more recent data are available for either systematic thrombolysis or catheter-induced thrombolysis in patients with DVTUE. It could therefore be reserved for those patients who, within 1 week following thrombus formation, are dependent on venous access for their dialysis or feeding lines or as an aggressive attempt to re-establish normal venous return in young patients with effort thrombosis. Urokinase and r-tPAa are the most commonly used drugs for local fibrinolysis. There is no consensus in the literature about the dose to be used, and most authors use the same dose as for local arterial fibrinolysis: a loading dose of 250,000 U/urokinase and between 50,000 and 100,000 U/h. The time to achieve total lysis in subclavian vein thrombosis is often much longer than for local arterial lysis, and could be up to 72 h. In cases of Paget–Schroetter syndrome, a first rib resection is recommended after successful lysis. Also, 3–6 months of oral anticoagulant therapy, such as warfarin sodium, should
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Fig. 7 a Patient with cancer following repeated courses of chemotherapy with bilateral catheter-related deep vein thrombosis of the upper extremities. b Mechanical thrombectomy on the right side, catheter passed through the thrombus mass. c Mechanical thrombectomy, result after three runs. d Mechanical thrombectomy, final result
be undertaken after lysis, especially after catheter-induced thrombosis [47–49]. Although there are only a few reports in the literature about fibrinolysis of subclavian vein thrombosis, the reported results are very good, with restoration of flow in more than 90% of cases [47–49]. Interventional techniques Although interventional techniques such as mechanical thrombectomy have been described in arterial, venous and dialysis shunt thrombosis, reports of this technique in DVTUE are minimal [50]. It is in this area that instant debulking or removal of thrombus, and thereby restoration of flow, could be very beneficial in selected cases. One of the problems with mechanical thrombectomy is that there is often a mismatch between the small working profile of the device and the larger vessel lumen. This means that total thrombus removal is often not achieved; however, in our experience, debulking with restoration of flow can be obtained. In chronic thrombosis, more than 1 week old, mechanical thrombectomy is not an option. Newer techniques such as ultrasound or hyperthermia-assisted fibrinolysis might of-
fer a solution, but the current experience is still minimal [51, 52]. As the diagnosis of post-thrombotic arm syndrome is still very much under debate, it is very doubtful whether patients with a primary upper extremity thrombosis will benefit from early mechanical thrombectomy. However, in those patients with secondary thrombosis, where maintenance of venous patency is mandatory for indwelling lines and life-support, early restoration of flow might be vital. In addition, preservation of a line can be achieved. There are no studies that have addressed this problem, except from some incidental reports [50]. What is clear from this experience is that the technique of venous mechanical thrombectomy is safe and easy to perform, with good instant results (Fig. 7). The technique involves puncture of a brachial vein and introduction of a 7-French sheath. After passage of a guide wire through the thrombus, a mechanical thrombectomy device can be used. Since a procedure over the wire is strongly advised and the risk of vessel wall damage should be as minimal as possible, rotating devices are not recommended. Any catheter based on the hydrodynamic Venturi effect, such as the Hydrolyser (Cordis, Roden, The Netherlands), the Oasis (Boston Scientific, USA) and the Angiojet (Possis, USA), can be used. Debulking and restoration of the vessel lumen
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should be followed by standard anticoagulant therapy. Randomised investigation of these techniques seems the next logical step in the treatment of secondary upper extremity thrombosis. Catheter-related stenosis is another problem that can be treated by PTA or stenting. There are reports showing very good results after stenting of the subclavian vein [53]. A flexible self-expandable oversized stent, like the Wallstent (Boston Scientific, USA), is recommended. However, for Paget–Schroetter syndrome, stents seem to be of little value with a high percentage of stent fracture [54]. Surgery Surgery was employed more commonly in earlier years, when the cause of thrombosis was thought to be related to thoracic inlet obstruction, i.e. extrinsic vein compression [55]. Surgical procedures in acute cases consist of removal of the first rib, clavicle and anterior scalene muscles to relieve subclavian vein compression [56]. Vein patch angioplasty was needed in recurrent, subacute, and chronic cases if the length of the stenosis or obstruction was more than 2 cm. However, in recent years the proportion of patients with effort or anatomical aetiology, i.e. primary thrombosis, has decreased and surgery has largely vanished as a therapeutic option. Surgery may be required in those patients where the venous system has been destroyed and where intravenous access is required, or it can be performed after anticoagulant or fibrinolytic therapy has failed in young patients with primary thrombosis.
Complications and long-term prognosis PE and post-thrombotic syndrome are two major complications of DVTUE. Although the significance of deep vein thrombosis of the arm has received less attention than deep leg vein thrombosis, subsequent PE occurs al-
Fig. 8 Possible diagnostic pathway for patients suspected of having deep vein thrombosis of the upper extremity (DVTUE; DCUS duplex colour ultrasonography). * = anticoagulant standard therapy
most as frequently as in patients with leg vein thrombosis, at a rate of 3–36%. However, only a minority of patients with PE have clinical symptoms and only a very small minority of cases are fatal [15]. Post-thrombotic syndrome, due to venous hypertension secondary to outflow obstruction, varies from mild oedema and discomfort to excessive pain, swelling and dysfunctioning of the arm. The frequency of post-thrombotic syndrome in patients with proven DVTUE ranges from a minimum of 4% in patients with severe complaints to a maximum of 22% in those with mild sequelae. Unfortunately, only a few studies exist on this subject [5, 14, 57]. This can be explained partly by the bad survival rate of cancer patients with catheter-related secondary thrombosis. One study, in which only late sequelae of patients with spontaneous primary thrombosis were studied, assessed severe or intolerable symptoms in 13% of patients [57]. However, no relation was seen between ultrasonographic sequelae and symptom severity scores. A recent study describes good clinical outcome in patients with effort thrombosis initially treated with anticoagulant therapy followed by additional angioplasty, stenting or surgery [58].
Conclusions, recommendations for management and prophylaxis DVTUE is an increasing clinical problem which requires immediate and accurate diagnostic techniques. The diagnosis of DVTUE should start with Duplex ultrasonography, as this is easily available and non-invasive. Non-compressibility of a normally compressible vein and/or visible thrombus is certain proof of the presence of DVTUE. However, several pitfalls exist and isolated flow abnormalities should not be accepted as proof for diagnosis. Furthermore, causes of venous compression should be noted. If ultrasonography is inconclusive or normal in cases of strong clinical suspicion of thrombosis, contrast venography should be performed. The implementation of MR venography or CT venography is
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Fig. 9 Algorithm for therapy of deep vein thrombosis of the upper extremities (based on this paper)
currently not warranted for routine clinical practice, but can be an alternative tool in individual cases and might play a more significant role in the near future. In cases of DVTUE and suspicion of pulmonary emboli, which can be present in 3–36% of patients, CT is mandatory. Figure 8 shows a possible diagnostic pathway for patients suspected of having DVTUE. Treatment of upper extremity thrombosis is aimed at preservation of anatomy for venous access, and prevention of (potentially fatal) PE. Treatment is dependent on
the cause, duration of thrombosis and clinical circumstances. For the majority of patients with primary or secondary upper extremity thrombosis, 5–7 days of heparin (or low-molecular-weight heparin) in combination with at least 3 months of oral anticoagulants is usually sufficient, also for prevention of PE and post-thrombotic syndrome. However, there is a tendency to more aggressive treatments with thrombolysis or mechanical thrombectomy in individual cases, especially in younger patients who are at risk of chronic venous insufficiency or in patients with near-fatal PE. Patients with primary effort thrombosis may benefit from anticoagulant therapy or fibrinolysis, followed by additional stenting or surgery in cases of underlying or persistent venous abnormality or external compression. If one contemplates line salvage in patients with catheter-related thrombosis, fibrinolytic therapy or mechanical thrombectomy could be considered. A possible algorithm for the treatment of primary and catheter-related DVTUE is shown in Fig. 9. The use of warfarin or low-molecular-weight heparin as prophylaxis for cancer patients with central venous catheters is still under evaluation [59]. Although lowdose anticoagulants do not usually prolong the clotting times substantially, for some patients in bad clinical condition they may be sufficient to cause excessive bleeding.
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