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The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults: A systematic review
Thrombosis Research (2006) 117, 609 — 614
intl.elsevierhealth.com/journals/thre
REVIEW ARTICLE
The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults: A systematic review Elyssa E. Elman a, Susan R. Kahn a,b,* a
Faculty of Medicine, McGill University, Montreal, Canada Center for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste. Catherine Rm. A-127, Montreal, Quebec, Canada H3T 1E2
b
Received 23 February 2005; received in revised form 9 May 2005; accepted 20 May 2005 Available online 6 July 2005
KEYWORDS Deep venous thrombosis; Upper extremity; Post-thrombotic syndrome; Adults; Review article
Abstract Background: Post-thrombotic syndrome is a chronic, potentially debilitating complication of deep vein thrombosis (DVT) of the lower extremity. Comparatively little is known about post-thrombotic syndrome after upper extremity DVT (UEDVT). Objective: To perform a systematic review of clinical studies that have examined the incidence, clinical features, risk factors and management of post-thrombotic syndrome after UEDVT. Methods: Using combinations of keywords venous thrombosis, postphlebitic syndrome, thrombophlebitis, arm swelling, post-thrombotic syndrome, UEDVT, Paget— Schroetter syndrome, thoracic outlet syndrome, axillary vein, subclavian vein, and central venous catheter, the MEDLINE database was searched for English language articles published between January 1967 and December 2004. Retrieval and review of articles were restricted to clinical studies in humans that described long-term outcomes after objectively confirmed UEDVT. Results: Seven studies were reviewed. The frequency of PTS after UEDVT ranges from 7—46% (weighted mean 15%). Residual thrombosis and axillosubclavian vein thrombosis appear to be associated with an increased risk of PTS, whereas catheter-associated UEDVT may be associated with a decreased risk. There is currently no validated, standardized scale to assess upper extremity PTS, and little consensus regarding the optimal management of this condition. Quality of life is
* Corresponding author. Center for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste. Catherine Rm. A-127, Montreal, Quebec, Canada H3T 1E2. Tel.: +1 340 8222 4667; fax: +1 514 340 7564. E-mail address: [email protected] (S.R. Kahn). 0049-3848/$ - see front matter D 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2005.05.029
610
E.E. Elman, S.R. Kahn impaired in patients with upper extremity PTS, especially after DVT of the dominant arm. Conclusions: PTS is a frequent complication of UEDVT, yet little is known regarding risk factors and optimal management. A standardized means of diagnosis would help to establish better management protocols. The impact of upper extremity PTS on quality of life should be further quantified. D 2005 Elsevier Ltd. All rights reserved.
Contents Introduction . . . . . . . . . . . . . . . . . . Methods. . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . Criteria used to diagnose PTS. . . . . . . Incidence of PTS after UEDVT. . . . . . . Risk factors for PTS after UEDVT . . . . . Management of upper extremity PTS . . Effect on patient function and quality of Conclusions and future direction . . . . . Acknowledgements . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . .
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Introduction Although most episodes of deep venous thrombosis (DVT) occur in the lower extremities, it has been estimated that 1—4% of cases involve the upper extremities [1,2]. Upper extremity deep vein thrombosis (UEDVT) is an increasingly common clinical problem due to the growing use of cardiac pacemaker implantation and central venous catheters for drug delivery in both in-patient and outpatient settings [3—7]. UEDVT can be classified into two etiologic groups: primary (includes idiopathic, effort-related or Paget—Schroetter syndrome and thoracic outlet syndrome) and secondary (provoked by central venous catheters, pacemakers or cancer) [8]. Secondary causes underlie most cases of UEDVT; in particular, it has been reported that central venous catheters account for about 75% of all cases [9]. Conversely, primary UEDVT is rare, occurring in only 2 / 100,000 persons per year [10]. The post-thrombotic syndrome (PTS) is a chronic, potentially debilitating complication of DVT of the lower extremity that is characterized by limb pain, heaviness, swelling, cramps, edema, varicosities and in severe cases, ulcers [11]. PTS has been estimated to develop in 20—50% of patients after lower extremity DVT [11], has adverse effects on quality of life [12] and incurs high costs [13]. However, it is less well known whether PTS also occurs after UEDVT. It can be appreciated that the development of PTS in an upper extremity could be burdensome and disabling, particularly if it oc-
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curred in the dominant arm. The objectives of this paper were to systematically review the published literature on the incidence, clinical features, predictors and management of PTS after UEDVT.
Methods A computerized search of the MEDLINE database from January 1967 to December 2004 was performed to identify English language articles on the PTS after upper extremity DVT. Various combinations of the search terms postphlebitic syndrome, post-thrombotic syndrome, thrombophlebitis or arm swelling, were combined with one or more of the search terms upper extremity deep venous thrombosis, venous thrombosis, axillary vein, subclavian vein, arm, effort thrombosis, Paget—Schroetter syndrome, upper extremity, thoracic outlet syndrome, central venous line or catheterization. The bibliographies of relevant articles were screened to obtain additional articles that were not retrieved by the MEDLINE search. We included articles that described a population of patients who had objectively confirmed UEDVT and in whom some description of chronic sequelae during long-term outcome was provided.
Results Our literature search revealed 7 articles that met our criteria for inclusion in this review. There were
Studies of the occurrence of post-thrombotic syndrome after upper extremity deep venous thrombosis
Author
Study type
UEDVT confirmed by
Patient population
PTS definition
Number of patients with UEDVT
Frequency of PTS (%)
Donayre 1986
Retrospective cohort
Venography
Persistent pain and edema
41
11 (28%)a
Hingorani 1997
Retrospective cohort
Duplex ultrasound
Swelling, pitting edema
170
11/156 (7%)b
Prandoni 1997
Prospective cohort
Venography
Confirmed axillosubclavian thrombosis Patients with confirmed acute UEDVT Consecutive patients with suspected UEDVT diagnosed with UEDVT
27
4 (15%)
Kreienberg 2001
Prospective cohort
Venography
Symptoms (heaviness, pain, paresthesia, functional limitation, and pruritus) and signs (edema, tenderness, skin induration, venous dilatation, redness, discoloration); considered severe if persisting manifestations impaired quality of life Arm swelling or pain
23
6 (26%)
Sabeti 2003
Retrospective cohort
Duplex ultrasound
95
9 (10%)
Prandoni 2004
Prospective cohort
Ultrasound or venography
53
13 (25%) 1 patient had severe PTS (2%)
Kahn 2005
Retrospective cohort
Duplex ultrasound
24
11 (46%)
432
65 (15%)
Total a b
Effort thrombosis (Paget—Schroetter syndrome) UEDVT treated in angiology department Consecutive patients with a 1st symptomatic UEDVT
Patients with confirmed UEDVT
Swelling, superficial varicose collateral veins Standardized scale of symptoms (heaviness, pain, itching, physical limitation, paresthesia) and signs (pretibial edema, skin induration, discoloration, venous ectasia, redness, pain during compression) Standardized scale (Villata) modified for upper extremity
The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults
Table 1
One patient was lost to follow-up. 14 patients were lost to follow-up.
611
612 3 prospective cohort studies and 4 retrospective cohort studies. A total of 432 patients were described (Table 1).
Criteria used to diagnose PTS There is no bgold standardQ test for the diagnosis of PTS [14], hence it is not surprising that definitions of upper extremity PTS vary significantly among authors. Various definitions that have been used (see Table 1) include pain and swelling of the affected arm; pain, swelling, edema, and functional limitation of the affected arm; heaviness, paresthesia, pruritis, venous hypertension, skin induration and functional limitation of the arm; swelling of the arm or hand and superficial varicose collateral veins, or simply mild swelling of the arm. Both Prandoni et al. [15] and Kahn et al. [16] used a modification of an existing lower extremity PTS scale [17] to diagnose upper extremity PTS that assigns points for symptoms (e.g. pain, cramps, heaviness, pruritus and paresthesia) and signs (e.g. edema, prominent veins on arm, prominent veins over shoulder or anterior chest wall, redness, tenderness, dependent cyanosis), then sums the points to arrive at a summative score. However, this scale has not been formally validated for the upper extremity, and there exists no scale that was specifically developed for use after UEDVT.
Incidence of PTS after UEDVT In a small group of patients with confirmed UEDVT, Prandoni et al. reported that the frequency of PTS, defined by the presence of symptoms (heaviness, pain, paresthesia, functional limitation and pruritus) and signs (edema, tenderness, induration of the skin, venous dilatation, redness and skin discoloration), was 15% at 2 years follow-up [18]. In a more recent prospective study by Prandoni et al., 53 patients with UEDVT (6 of which were catheter related) were treated with standard heparin and warfarin for 3 months and were followed for an average of 36 months [15]. Of these, 13 (24.5%) developed PTS, which was diagnosed using a standardized scale that assessed signs and symptoms. Only one patient developed severe PTS. Hingorani et al. retrospectively assessed 170 patients with confirmed UEDVT (110 were catheter or pacemaker related). After a mean follow-up of 13 months, 7% of patients had PTS, which was defined as swelling and pitting edema of the arm [19]. In a retrospective study by Donayre et al., 41 patients with axillosubclavian DVT were assessed after a mean follow-up of 21 months.
E.E. Elman, S.R. Kahn Overall, the rate of PTS was 28%; however no patient with catheter-associated DVT developed PTS [20]. Sabeti et al. investigated long-term clinical outcomes in a retrospective study of 95 in-patients with subclavian—axillary thrombosis who were treated with urokinase followed by oral anticoagulation or oral anticoagulation alone [21]. After a median follow-up of 40 months, nine (10%) had upper extremity PTS, defined as swelling of the hand or arm and superficial varicose collateral veins. Although as demonstrated by repeat ultrasound the thrombolysis group experienced a higher recanalization rate, the frequency of symptomatic PTS in both treatment groups was similar. Kreienberg et al. evaluated 23 patients with effortrelated thrombosis (Paget—Schroetter syndrome) of the subclavian vein with or without axillary vein thrombosis [22]. All patients underwent percutaneous transluminal angioplasty. This treatment was successful in 9 patients, none of whom subsequently developed chronic arm swelling. However, among the 14 patients who developed subsequent vein restenosis, 6 (26%) reported chronic mild arm swelling. Finally, in a retrospective study of 24 patients with objectively diagnosed UEDVT performed by our group, 46% had developed PTS after a median follow-up of 13 months [16]. In this study, PTS was diagnosed using a modified version of a validated lower extremity PTS scale [17]. Hence, although few studies have reported on the incidence of PTS following UEDVT and results are difficult to compare due to variations in followup time and definitions of PTS, the overall frequency of PTS after UEDVT appears to be in the range of 7—46%, with a weighted mean frequency across studies of 15%. PTS may be less frequent after catheter-associated UEDVT that after UEDVT of other etiology.
Risk factors for PTS after UEDVT To date, little is known regarding risk factors for the development of PTS after UEDVT. Prandoni et al. reported that residual thrombosis on ultrasound after UEDVT is associated with a four-fold increased risk of PTS [15]. Furthermore, axillary and subclavian vein thromboses appear to be related to the development of PTS more than other sites (hazard ratio 2.9). As is the case for lower extremity PTS, it is plausible that factors that increase the risk of ipsilateral DVT recurrence could also increase the risk of PTS. In a case—control study by Martinelli et al. of 115 patients with primary UEDVT and 797 controls, cases with thrombophilia (e.g. factor V Leiden, prothrombin G20210A, antithrombin, protein C, and protein S deficiency) were more likely
The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults to experience recurrent symptomatic DVT than those without thrombophilia (4.4%/year vs. 1.6%/ year, respectively) [23]. However, whether the incidence of PTS was similarly increased was not reported. As discussed earlier, catheter-associated UEDVT may be associated with a reduced risk of PTS [20], perhaps because removal of the catheter reduces vessel injury. It is not known whether thrombolytic treatment of the UEDVT leads to lower rates of PTS than standard anticoagulation, or whether duration, intensity or specific type of anticoagulant therapy used to treat the initial UEDVT influence the development or worsening of the post-thrombotic syndrome.
Management of upper extremity PTS Elastic compression stocking are often used to control symptoms and swelling associated with lower extremity PTS [14]. Little is known, however, about the effectiveness of compression socks or sleeves applied to the arm for the management of upper extremity PTS, and what their ideal strength or length should be. Among the articles we reviewed, there were few references to the management of established upper extremity PTS, however Joffe and Goldhaber recommend the use of graduated compression sleeves for all symptomatic patients with acute UEDVT to prevent the development of chronic venous insufficiency, especially in younger patients [8]. To date, however, there have been no trials to test the effectiveness of compression therapy for the management of PTS of the upper extremity.
Effect on patient function and quality of life Only one study examined the effect of PTS of the upper extremity on patient function and quality of life. Kahn et al. evaluated 24 patients with objectively confirmed UEDVT at a median of 13 months following diagnosis. Those that had PTS had significantly worse generic and venous disease specific quality of life and greater functional disability (as measured by the DASH questionnaire) than those without PTS, and the overall impact of PTS appeared to be more severe when the UEDVT occurred in the dominant arm [16].
Conclusions and future direction Although large prospective studies with clearly defined populations of patients with UEDVT and validated diagnostic criteria for PTS are lacking, it appears from the existing data that PTS is a fairly
613
frequent complication of UEDVT (mean 15%; range 7—46%). As the incidence of UEDVT is on the rise due to the increasing use of cardiac pacemaker implantation and central venous catheters for drug delivery, further large prospective studies to more precisely estimate the incidence, timing and risk factors for PTS after UEDVT would be of value. Also, development and validation of a standardized scale specific for PTS of the upper extremity would help standardize the diagnosis of this condition and consequently will help to establish better management protocols. In addition, the impact of upper extremity PTS on patients’ quality of life, daily symptoms, and ability to carry out activities of daily living, particularly if the dominant arm is affected, should be further quantified.
Acknowledgements Dr. Kahn is the recipient of a Clinical Research Scientist award of the Fonds de la Recherche en Sante ´ du Que ´bec.
References [1] Coon WW, Willis III PW. Thrombosis of axillary and subclavian veins. Arch Surg 1967;94:657 – 63. [2] Horattas MC, Wright DJ, Fenton AH, Evans DM, Oddi MA, Kamienski RW, et al. Changing concepts of deep venous thrombosis of the upper extremity—report of a series and review of the literature. Surgery 1988;104:561 – 7. [3] Hill SL, Berry RE. Subclavian vein thrombosis: a continuing challenge. Surgery 1990;108:1 – 9. [4] Chastre J, Cornud F, Bouchama A, Viau F, Benacerraf R, Gibert C. Thrombosis as a complication of pulmonaryartery catheterization via the internal jugular vein: prospective evaluation by phlebography. N Engl J Med 1982;306:278 – 81. [5] Timsit JF, Farkas JC, Boyer JM, Martin JB, Misset B, Renaud B, et al. Central vein catheter-related thrombosis in intensive care patients: incidence, risks factors, and relationship with catheter-related sepsis. Chest 1998;114: 207 – 13. [6] Martin C, Viviand X, Saux P, Gouin F. Upper-extremity deep vein thrombosis after central venous catheterization via the axillary vein. Crit Care Med 1999;27:2626 – 9. [7] Hendler MF, Meschengieser SS, Blanco AN, Alberto MF, Salviu MJ, Gennari L, et al. Primary upper-extremity deep vein thrombosis: high prevalence of thrombophilic defects. Am J Hematol 2004;76:330 – 7. [8] Joffe HV, Goldhaber SZ. Upper-extremity deep vein thrombosis. Circulation 2002;106:1874 – 80. [9] Marinella MA, Kathula SK, Markert RJ. Spectrum of upperextremity deep venous thrombosis in a community teaching hospital. Heart Lung 2000;29:113 – 7. [10] Becker DM, Philbrick JT, Walker FB. Axillary and subclavian venous thrombosis. Prognosis and treatment. Arch Intern Med 1991;151:1934 – 43.
614 [11] Kahn SR, Ginsberg JS. The post-thrombotic syndrome: current knowledge, controversies, and directions for future research. Blood Rev 2002;16:155 – 65. [12] Kahn SR, Hirsch A, Shrier I. Effect of post-thrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 2002;162:1144 – 8. [13] Bergqvist D, Jendteg S, Johansen L, Persson U, Odegaard K. Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined patient population in Sweden. Ann Intern Med 1997;126:454 – 7. [14] Kahn SR, Ginsberg JS. Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Int Med 2004;164:17 – 26. [15] Prandoni P, Bernardi E, Marchiori A, Lensing AW, Prins MH, Villalta S, et al. The long term clinical course of acute deep vein thrombosis of the arm: prospective cohort study. BMJ 2004;329:484 – 5. [16] Kahn S, Elman E, Bornais C, Blostein M, Wells P. Postthrombotic syndrome, functional disability and quality of life after upper extremity deep venous thrombosis in adults. Thromb Haemost 2005;93:499 – 502. [17] Villalta S, Bagatella P, Piccioli A, Lensing A, Prins M, Prandoni P. Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome (abstract). Haemostasis 1994;24:158a.
E.E. Elman, S.R. Kahn [18] Prandoni P, Polistena P, Bernardi E, Cogo A, Casara D, Verlato F, et al. Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med 1997;157:57 – 62. [19] Hingorani A, Ascher E, Lorenson E, DePippo P, SallesCunha S, Scheinman M, 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 – 60. [20] Donayre CE, White GH, Mehringer SM, Wilson SE. Pathogenesis determines late morbidity of axillosubclavian vein thrombosis. Am J Surg 1986;152:179 – 84. [21] Sabeti S, Schillinger M, Mlekusch W, Haumer M, Ahmadi R, Minar E. Treatment of subclavian—axillary vein thrombosis: long-term outcome of anticoagulation versus systemic thrombolysis. Thromb Res 2002;108:279 – 85. [22] Kreienberg PB, Chang BB, Darling III RC, Roddy SP, Paty PS, Lloyd WE, et al. Long-term results in patients treated with thrombolysis, thoracic inlet decompression, and subclavian vein stenting for Paget—Schroetter syndrome. J Vasc Surg 2001;33:S100—5. [23] Martinelli I, Battaglioli T, Bucciarelli P, Passamonti SM, Mannucci PM. Risk factors and recurrence rate of primary deep vein thrombosis of the upper extremities. Circulation 2004;110:566 – 70.
intl.elsevierhealth.com/journals/thre
REVIEW ARTICLE
The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults: A systematic review Elyssa E. Elman a, Susan R. Kahn a,b,* a
Faculty of Medicine, McGill University, Montreal, Canada Center for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste. Catherine Rm. A-127, Montreal, Quebec, Canada H3T 1E2
b
Received 23 February 2005; received in revised form 9 May 2005; accepted 20 May 2005 Available online 6 July 2005
KEYWORDS Deep venous thrombosis; Upper extremity; Post-thrombotic syndrome; Adults; Review article
Abstract Background: Post-thrombotic syndrome is a chronic, potentially debilitating complication of deep vein thrombosis (DVT) of the lower extremity. Comparatively little is known about post-thrombotic syndrome after upper extremity DVT (UEDVT). Objective: To perform a systematic review of clinical studies that have examined the incidence, clinical features, risk factors and management of post-thrombotic syndrome after UEDVT. Methods: Using combinations of keywords venous thrombosis, postphlebitic syndrome, thrombophlebitis, arm swelling, post-thrombotic syndrome, UEDVT, Paget— Schroetter syndrome, thoracic outlet syndrome, axillary vein, subclavian vein, and central venous catheter, the MEDLINE database was searched for English language articles published between January 1967 and December 2004. Retrieval and review of articles were restricted to clinical studies in humans that described long-term outcomes after objectively confirmed UEDVT. Results: Seven studies were reviewed. The frequency of PTS after UEDVT ranges from 7—46% (weighted mean 15%). Residual thrombosis and axillosubclavian vein thrombosis appear to be associated with an increased risk of PTS, whereas catheter-associated UEDVT may be associated with a decreased risk. There is currently no validated, standardized scale to assess upper extremity PTS, and little consensus regarding the optimal management of this condition. Quality of life is
* Corresponding author. Center for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste. Catherine Rm. A-127, Montreal, Quebec, Canada H3T 1E2. Tel.: +1 340 8222 4667; fax: +1 514 340 7564. E-mail address: [email protected] (S.R. Kahn). 0049-3848/$ - see front matter D 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2005.05.029
610
E.E. Elman, S.R. Kahn impaired in patients with upper extremity PTS, especially after DVT of the dominant arm. Conclusions: PTS is a frequent complication of UEDVT, yet little is known regarding risk factors and optimal management. A standardized means of diagnosis would help to establish better management protocols. The impact of upper extremity PTS on quality of life should be further quantified. D 2005 Elsevier Ltd. All rights reserved.
Contents Introduction . . . . . . . . . . . . . . . . . . Methods. . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . Criteria used to diagnose PTS. . . . . . . Incidence of PTS after UEDVT. . . . . . . Risk factors for PTS after UEDVT . . . . . Management of upper extremity PTS . . Effect on patient function and quality of Conclusions and future direction . . . . . Acknowledgements . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . .
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Introduction Although most episodes of deep venous thrombosis (DVT) occur in the lower extremities, it has been estimated that 1—4% of cases involve the upper extremities [1,2]. Upper extremity deep vein thrombosis (UEDVT) is an increasingly common clinical problem due to the growing use of cardiac pacemaker implantation and central venous catheters for drug delivery in both in-patient and outpatient settings [3—7]. UEDVT can be classified into two etiologic groups: primary (includes idiopathic, effort-related or Paget—Schroetter syndrome and thoracic outlet syndrome) and secondary (provoked by central venous catheters, pacemakers or cancer) [8]. Secondary causes underlie most cases of UEDVT; in particular, it has been reported that central venous catheters account for about 75% of all cases [9]. Conversely, primary UEDVT is rare, occurring in only 2 / 100,000 persons per year [10]. The post-thrombotic syndrome (PTS) is a chronic, potentially debilitating complication of DVT of the lower extremity that is characterized by limb pain, heaviness, swelling, cramps, edema, varicosities and in severe cases, ulcers [11]. PTS has been estimated to develop in 20—50% of patients after lower extremity DVT [11], has adverse effects on quality of life [12] and incurs high costs [13]. However, it is less well known whether PTS also occurs after UEDVT. It can be appreciated that the development of PTS in an upper extremity could be burdensome and disabling, particularly if it oc-
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610 610 610 612 612 612 613 613 613 613 613
curred in the dominant arm. The objectives of this paper were to systematically review the published literature on the incidence, clinical features, predictors and management of PTS after UEDVT.
Methods A computerized search of the MEDLINE database from January 1967 to December 2004 was performed to identify English language articles on the PTS after upper extremity DVT. Various combinations of the search terms postphlebitic syndrome, post-thrombotic syndrome, thrombophlebitis or arm swelling, were combined with one or more of the search terms upper extremity deep venous thrombosis, venous thrombosis, axillary vein, subclavian vein, arm, effort thrombosis, Paget—Schroetter syndrome, upper extremity, thoracic outlet syndrome, central venous line or catheterization. The bibliographies of relevant articles were screened to obtain additional articles that were not retrieved by the MEDLINE search. We included articles that described a population of patients who had objectively confirmed UEDVT and in whom some description of chronic sequelae during long-term outcome was provided.
Results Our literature search revealed 7 articles that met our criteria for inclusion in this review. There were
Studies of the occurrence of post-thrombotic syndrome after upper extremity deep venous thrombosis
Author
Study type
UEDVT confirmed by
Patient population
PTS definition
Number of patients with UEDVT
Frequency of PTS (%)
Donayre 1986
Retrospective cohort
Venography
Persistent pain and edema
41
11 (28%)a
Hingorani 1997
Retrospective cohort
Duplex ultrasound
Swelling, pitting edema
170
11/156 (7%)b
Prandoni 1997
Prospective cohort
Venography
Confirmed axillosubclavian thrombosis Patients with confirmed acute UEDVT Consecutive patients with suspected UEDVT diagnosed with UEDVT
27
4 (15%)
Kreienberg 2001
Prospective cohort
Venography
Symptoms (heaviness, pain, paresthesia, functional limitation, and pruritus) and signs (edema, tenderness, skin induration, venous dilatation, redness, discoloration); considered severe if persisting manifestations impaired quality of life Arm swelling or pain
23
6 (26%)
Sabeti 2003
Retrospective cohort
Duplex ultrasound
95
9 (10%)
Prandoni 2004
Prospective cohort
Ultrasound or venography
53
13 (25%) 1 patient had severe PTS (2%)
Kahn 2005
Retrospective cohort
Duplex ultrasound
24
11 (46%)
432
65 (15%)
Total a b
Effort thrombosis (Paget—Schroetter syndrome) UEDVT treated in angiology department Consecutive patients with a 1st symptomatic UEDVT
Patients with confirmed UEDVT
Swelling, superficial varicose collateral veins Standardized scale of symptoms (heaviness, pain, itching, physical limitation, paresthesia) and signs (pretibial edema, skin induration, discoloration, venous ectasia, redness, pain during compression) Standardized scale (Villata) modified for upper extremity
The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults
Table 1
One patient was lost to follow-up. 14 patients were lost to follow-up.
611
612 3 prospective cohort studies and 4 retrospective cohort studies. A total of 432 patients were described (Table 1).
Criteria used to diagnose PTS There is no bgold standardQ test for the diagnosis of PTS [14], hence it is not surprising that definitions of upper extremity PTS vary significantly among authors. Various definitions that have been used (see Table 1) include pain and swelling of the affected arm; pain, swelling, edema, and functional limitation of the affected arm; heaviness, paresthesia, pruritis, venous hypertension, skin induration and functional limitation of the arm; swelling of the arm or hand and superficial varicose collateral veins, or simply mild swelling of the arm. Both Prandoni et al. [15] and Kahn et al. [16] used a modification of an existing lower extremity PTS scale [17] to diagnose upper extremity PTS that assigns points for symptoms (e.g. pain, cramps, heaviness, pruritus and paresthesia) and signs (e.g. edema, prominent veins on arm, prominent veins over shoulder or anterior chest wall, redness, tenderness, dependent cyanosis), then sums the points to arrive at a summative score. However, this scale has not been formally validated for the upper extremity, and there exists no scale that was specifically developed for use after UEDVT.
Incidence of PTS after UEDVT In a small group of patients with confirmed UEDVT, Prandoni et al. reported that the frequency of PTS, defined by the presence of symptoms (heaviness, pain, paresthesia, functional limitation and pruritus) and signs (edema, tenderness, induration of the skin, venous dilatation, redness and skin discoloration), was 15% at 2 years follow-up [18]. In a more recent prospective study by Prandoni et al., 53 patients with UEDVT (6 of which were catheter related) were treated with standard heparin and warfarin for 3 months and were followed for an average of 36 months [15]. Of these, 13 (24.5%) developed PTS, which was diagnosed using a standardized scale that assessed signs and symptoms. Only one patient developed severe PTS. Hingorani et al. retrospectively assessed 170 patients with confirmed UEDVT (110 were catheter or pacemaker related). After a mean follow-up of 13 months, 7% of patients had PTS, which was defined as swelling and pitting edema of the arm [19]. In a retrospective study by Donayre et al., 41 patients with axillosubclavian DVT were assessed after a mean follow-up of 21 months.
E.E. Elman, S.R. Kahn Overall, the rate of PTS was 28%; however no patient with catheter-associated DVT developed PTS [20]. Sabeti et al. investigated long-term clinical outcomes in a retrospective study of 95 in-patients with subclavian—axillary thrombosis who were treated with urokinase followed by oral anticoagulation or oral anticoagulation alone [21]. After a median follow-up of 40 months, nine (10%) had upper extremity PTS, defined as swelling of the hand or arm and superficial varicose collateral veins. Although as demonstrated by repeat ultrasound the thrombolysis group experienced a higher recanalization rate, the frequency of symptomatic PTS in both treatment groups was similar. Kreienberg et al. evaluated 23 patients with effortrelated thrombosis (Paget—Schroetter syndrome) of the subclavian vein with or without axillary vein thrombosis [22]. All patients underwent percutaneous transluminal angioplasty. This treatment was successful in 9 patients, none of whom subsequently developed chronic arm swelling. However, among the 14 patients who developed subsequent vein restenosis, 6 (26%) reported chronic mild arm swelling. Finally, in a retrospective study of 24 patients with objectively diagnosed UEDVT performed by our group, 46% had developed PTS after a median follow-up of 13 months [16]. In this study, PTS was diagnosed using a modified version of a validated lower extremity PTS scale [17]. Hence, although few studies have reported on the incidence of PTS following UEDVT and results are difficult to compare due to variations in followup time and definitions of PTS, the overall frequency of PTS after UEDVT appears to be in the range of 7—46%, with a weighted mean frequency across studies of 15%. PTS may be less frequent after catheter-associated UEDVT that after UEDVT of other etiology.
Risk factors for PTS after UEDVT To date, little is known regarding risk factors for the development of PTS after UEDVT. Prandoni et al. reported that residual thrombosis on ultrasound after UEDVT is associated with a four-fold increased risk of PTS [15]. Furthermore, axillary and subclavian vein thromboses appear to be related to the development of PTS more than other sites (hazard ratio 2.9). As is the case for lower extremity PTS, it is plausible that factors that increase the risk of ipsilateral DVT recurrence could also increase the risk of PTS. In a case—control study by Martinelli et al. of 115 patients with primary UEDVT and 797 controls, cases with thrombophilia (e.g. factor V Leiden, prothrombin G20210A, antithrombin, protein C, and protein S deficiency) were more likely
The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults to experience recurrent symptomatic DVT than those without thrombophilia (4.4%/year vs. 1.6%/ year, respectively) [23]. However, whether the incidence of PTS was similarly increased was not reported. As discussed earlier, catheter-associated UEDVT may be associated with a reduced risk of PTS [20], perhaps because removal of the catheter reduces vessel injury. It is not known whether thrombolytic treatment of the UEDVT leads to lower rates of PTS than standard anticoagulation, or whether duration, intensity or specific type of anticoagulant therapy used to treat the initial UEDVT influence the development or worsening of the post-thrombotic syndrome.
Management of upper extremity PTS Elastic compression stocking are often used to control symptoms and swelling associated with lower extremity PTS [14]. Little is known, however, about the effectiveness of compression socks or sleeves applied to the arm for the management of upper extremity PTS, and what their ideal strength or length should be. Among the articles we reviewed, there were few references to the management of established upper extremity PTS, however Joffe and Goldhaber recommend the use of graduated compression sleeves for all symptomatic patients with acute UEDVT to prevent the development of chronic venous insufficiency, especially in younger patients [8]. To date, however, there have been no trials to test the effectiveness of compression therapy for the management of PTS of the upper extremity.
Effect on patient function and quality of life Only one study examined the effect of PTS of the upper extremity on patient function and quality of life. Kahn et al. evaluated 24 patients with objectively confirmed UEDVT at a median of 13 months following diagnosis. Those that had PTS had significantly worse generic and venous disease specific quality of life and greater functional disability (as measured by the DASH questionnaire) than those without PTS, and the overall impact of PTS appeared to be more severe when the UEDVT occurred in the dominant arm [16].
Conclusions and future direction Although large prospective studies with clearly defined populations of patients with UEDVT and validated diagnostic criteria for PTS are lacking, it appears from the existing data that PTS is a fairly
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frequent complication of UEDVT (mean 15%; range 7—46%). As the incidence of UEDVT is on the rise due to the increasing use of cardiac pacemaker implantation and central venous catheters for drug delivery, further large prospective studies to more precisely estimate the incidence, timing and risk factors for PTS after UEDVT would be of value. Also, development and validation of a standardized scale specific for PTS of the upper extremity would help standardize the diagnosis of this condition and consequently will help to establish better management protocols. In addition, the impact of upper extremity PTS on patients’ quality of life, daily symptoms, and ability to carry out activities of daily living, particularly if the dominant arm is affected, should be further quantified.
Acknowledgements Dr. Kahn is the recipient of a Clinical Research Scientist award of the Fonds de la Recherche en Sante ´ du Que ´bec.
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