5/5/15. Overview. Deep vein thrombosis of the upper extremity (UEDVT) Classification of UEDVT Epidemiology. Primary UEDVT.

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1 Deep vein thrombosis of the upper extremity (UEDVT) Hong H. Keo, MD, MSc Angiologie Kantonsspital Aarau Symposium venöse Insuff. und arterielle Gefässerkr. Glarus Overview Epidemiology Classification/Risk factors Clinical manifestations Complications Diagnostic work-up Managment of UEDVT Catheter associated UEDVT Paget-Schroetter Syndrome Summary of Management Classification of UEDVT Epidemiology UEDVT account for ~ 10% of all DVT In population based study: Annual incidence of 16/ Incidence is rising due to increasing use of indwelling central venous catheters Anatomic Definition: Proximal UEDVT: DVT involving the axillary or more proximal deep veins Distal UEDVT: DVT of brachial and more distal deep veins Etiologic Definition: Primary UEDVT Secondary UEDVT Important difference for management Joffe HV, Kucher N, et al.circulation.2004;110: Munoz FJ, et al. Chest. 2008;133: ; Spencer FA, et al. Am J Med. 2007;120: Primare UEDVT Idiopathic UEDVT Primary UEDVT Effort-related UEDVT = Paget-Schroetter Syndrome No obvious risk factor or underlying venous thoracic outlet syndrome (VTOS) can be identified However: The rate of thrombophilia is higher in idiopathic than in effortrelated or catheter-associated UEDVT In a small cohort study of 38 patients with presumed idiopathic UEDVT, nine (23.7% vs 11.1% for lower extremity DVT) were diagnosed with cancer (predominantly lung cancer and lymphoma) during the one year follow-up period, of whom most were discovered during the first week of hospital admission. Linnemann B et al. Thromb Haemost. 2008;100: Girolami A et al. Blood Coagul Fibrinolysis. 1999;10: More frequent than idiopathic UEDVT More frequent in men Nearly all patients have underlying VTOS Typical history: Occurs in otherwise healthy, young men with a history of vigorous exercise with the arm/shoulder or overhead activities (playing badminton, tennis, weightlifting, pitching a baseball, painting, car repair, etc) within the last 24 hours of the inciting event. Pathophysiology: Repetitive microtrauma to the vessel intima of the subclavian vein with subsequent activation of the coagulation cascade Illig KA, Doyle AJ. J Vasc Surg. 2010;51:

2 Classification of Thoracic Outlet Syndrome Venous thoracic outlet syndrome VTOS Narrowing of the anterior part of the thoracic outlet region, limited: antero-medially: by the intersection of the clavicle and first rib (including the subclavian muscle/ tendon and the costoclavicular ligament), postero-laterally: by the anterior scalene muscle Rem: Cervical ribs as a classic cause for neurogenic or arterial thoracic outlet syndromes are not of relevance for the development of VTOS Illig KA, Doyle AJ. J Vasc Surg. 2010;51: Illig KA, Doyle AJ. J Vasc Surg. 2010;51: Secondary UEDVT Catheter-associated UEDVT Definition: UEDVT in the presence of known endogenous or exogenous risk factor Most important risk factor: Central venous catheters Second most important risk factor: Cancer Mechanisms: cancer-induced prothrombotic state venous stasis due to direct vein compression or infiltration catheter- and treatment-related Other risk factors Surgery, immobilization of the arm (plaster cast), oral contraceptive use, and personal or family history of DVT Kucher N. N Engl J Med. 2011;364: Account for up to 50% of all UEDVT Indwelling central venous catheters (CVC) or port systems > pacemaker or defibrillator leads Incidence of UEDVT after CVC placement: clinically overt: varies between 5 to 28% with systematic screening: in up to 66% of cancer patients Peripherally inserted central catheters (PICC) Similar to CVC with a reported incidence 3 to 58% Joffe HV, Kucher N, et al. Circulation.2004;110: Lokich JJ, et al. Cancer. 1983;52: Karthaus M, et al.ann Oncol. 2006;17: Verso M, et al. J Clin Oncol. 2003;21: Evans RS, et al.chest. 2010;138: Risk factors for Catheterassociated UEDVT Clinical manifestations Symptoms Metaanalysis: Individual data of 12 prospective studies with 5636 cancer patients and 425 catheter-associated UEDVT Typically vague arm, shoulder or neck discomfort or pain, and swelling of the affected arm symptoms frequently improve with rest or elevation of the arm Symptoms might be mild or even completely absent especially in case of catheter-related UEDVT inability to draw blood from the catheter or fever due to catheter infection might be the presenting problem Saber W, et al.jth. 2011;9:

3 Clinical manifestations Signs Clinical manifestations Arm and hand edema Mild cyanosis of the involved extremity Visible collateral veins over the shoulder or upper arm Palpable tender cord Low fever attributable to the thrombosis or underlying malignancy and higher fever in case of septic thrombophlebitis Symptoms and signs for UEDVT are non-specific need to be confirmed/excluded with objective imaging testing Diagnosis Clinical manifestations Complications of UEDVT In general complications less frequent than for LEDVT Symptomatic pulmonary embolism Dilatation of subcutaneous collateral veins in a patient with left-sided upper extremity deep venous thrombosis Recurrence at 12 months 2-4% 6% 7-47% 20-50% 11% 7% After UEDVT: most occur during the first 6 months After LEDVT: recurrence frequently occurs beyond 6 months Engelberger & Kucher in press Spencer FA, et al. Am J Med. 2007;120: Post-thrombotic syndrome after UEDVT Complication rate depends on type of UEDVT: 15%-29% Temporal profile of recurrence seems to be different Complications of UEDVT LEDVT 2%-9% Post-thrombotic syndrome Overall 3 month mortality UEDVT Distal UEDVT considered to be at low risk for embolic complications or PTS Lower rates of PE with primary UEDVT compared to catheterassociated UEDVT No standardized tool for Dx of upper extremity PTS Quality of life particularly reduced if dominant arm affected Catheter-associated UEDVT with a reduced risk of PTS Risk of recurrent UEDVT: : cancer, female gender, high BMI, and possibly thrombophilia : CVC at the time of first thrombosis is associated with a lower risk if the catheter is removed Monreal M, et al. Chest. 1991;99: Flinterman LE, et al. Circulation. 2008;118: Martinelli I, et al. Circulation. 2004;110: Jones MA, et al. JVS.2010;51: Residual thrombosis at 6 months and axillosubclavian vein thrombosis increases the risk However, in recent study no correlation between hemodynamic or morphologic duplexsonographic findings and the development of PTS In patients with thrombosis due to VTOS, up to 53% of patients treated with anticoagulation alone complain of "non-negligible" PTS after a mean follow up of 5 years 1Kahn SR, et al.thromb Haemost. 2005;93: Persson LM, et al. JVS. 2006;43: E, et al.ann Intern Med. 1999;131: Heron 3

4 Diagnostic work-up No validated diagnostic strategy like for LEDVT Clinical prediction rule Diagnostic work-up D-dimer One small study with 52 consecutive patients 23 with cancer, 18 with CVC Results: Sensitivity of 100% (95% CI, %) Specificity of 14% (95% CI,4 29%) NPV 100%, PPV 32% Conclusion: due to high prevalence of comorbidities (cancer etc) D-dimer of limited value possibly useful in patients with suspected primary UEDVT Constans J, et al. Thromb Haemost. 2008;99: Merminod T, et al. Blood Coagul Fibrinolysis. 2006;17: Duplexsonography Other imaging studies Has replaced venography as initial diagnostic modality Recent systematic review: compression ultrasonography: Sensitivity 97% (95% CI, %) Specificity 96% (95% CI, %) Use of Color Doppler helpful for the evaluation of the proximal subclavian and innominate veins if the physiological variability of the Doppler flow with normal respiration or with the Valsalva maneuver is reduced/absent additional imaging required Contrast-enhanced CT and MRI only limited data available useful to diagnose proximal UEDVT diagnose concomitant pathologies, including cancer, adenopathy, or anatomic abnormalities suggestive of the VTOS Venography Goldstandard mainly used for endovascular or surgical therapy Di Nisio M, et al. J Thromb Haemost. 2010;8: Nisio M, et al. J Thromb Haemost. 2010;8: Diagnosis of UEDVT: 9th ACCP Diagnosis of UEDVT: 9th ACCP Bates SM, et al. Chest. 2012;141:e351S-418S Bates SM, et al. Chest. 2012;141:e351S-418S 4

5 Treatment Aims: alleviate symptoms prevent progression of thrombosis reduce the risk of PE, recurrence, and PTS. Most recommendations for the management of UEDVT were derived from data of patients with LEDVT Anticoagulation No RCT for treatment of UEDVT Rationale for Anticoagulation 1) UEDVT causes acute symptoms, can cause PE (including fatal episodes), and is associated with PTS 2) Observational studies support its use; and 3) there is strong evidence for benefit in patients with leg DVT. Anticoagulation for UEDVT: 9th ACCP a) Initial therapy Anticoagulation for UEDVT: 9th ACCP b) Long-term Anticoagulation 1 1 Anticoagulation for UEDVT: 9th ACCP b) Long-term Anticoagulation Catheter intervention Early thrombus removal and restoration of venous patency primarily aims at reducing the risk of PTS No randomized controlled studies have evaluated catheter directed thrombolysis (CDT) vs anticoagulation alone in UEDVT Retrospective study of 30 UEDVT patients CDT with r-tpa at a median dose of 52 mg, median time of 70 hours, Results: > 50% clot lysis in 97 % patients major bleeding complications in 9% mild PTS in 21% 1 Vik A, et al.cardiovasc Intervent Radiol. 2009;32:

6 Catheter intervention: 9th ACCP We believe that thrombolysis should be considered only in patients who meet all of the following criteria: severe symptoms, thrombus involving most of the subclavian vein and the axillary vein, symptoms for < 14 days, good functional status, life expectancy of >= 1 year, and low risk for bleeding Surgical therapy for UEDVT Surgical therapy, including thrombectomy, venoplasty or venous bypass in the absence of VTOS should be reserved to refractory cases as these procedures are invasive, carry the risk of anesthesia and may be complicated by phrenic nerve or brachial plexus lesions, lymphatic fistula, and hemopneumothorax Joffe HV, et al. Circulation. 2002;106: Schneider D, et al. J Vasc Surg. 2004;40: Catheter associated UEDVT Catheter associated UEDVT Save to leave catheter in place? In a cohort study of 74 cancer patients with symptomatic catheter associated UEDVT treated with anticoagulation alone 57% had a functional catheter at 3 months 43% had the catheter removed but none of them because of catheter failure or recurrent DVT If a catheter is occluded an attempt to restore patency can be performed by instillation of thrombolytics, e.g. one or two doses of 2 mg of r-tpa 2 Consider catheter removal if: Catheter malfunction or infection Contraindication to anticoagulation Persistent symptoms or signs of UEDVT during initial treatment Catheter no longer needed The optimal timing of catheter removal has not been evaluated but it is appropriate for most cases to remove the catheter after 3 to 5 days of anticoagulant therapy Kovacs MJ, et al.j Thromb Haemost. 2007;5: Semba CP, et al. J Vasc Interv Radiol. 2002;13: Kucher N. N Engl J Med. 2011;364: Catheter associated UEDVT: 9th ACCP Catheter associated UEDVT: 9th ACCP 6

7 Paget-Schroetter Syndrome A multidisciplinary therapeutic approach 1 anticoagulation therapy, +/-catheter-based thrombolysis and +/- subsequent surgical correction of VTOS Surgical decompression involves resection of the first rib and costoclavicular ligament, anterior scalenectomy, and venolysis. Optimal timing of surgical decompression controversial immediately after CDT versus 1 to 3 months thereafter Early decompression: +: effective and safe with earlier return to previous activity 2 - : possible overtreatment 3 1 Illig KA, Doyle AJ. J Vasc Surg. 2010;51: Angle N, et al. Ann Vasc Surg. 2001;15: Lee WA, et al. J Vasc Surg. 2000;32: Paget-Schroetter Syndrome In case of residual venous stenosis? Angioplasty with or without stenting remains controversial In a small cohort of 23 patients treated by angioplasty after surgical decompression Venous patency after follow up of 4 years " 100% in patients treated by angioplasty " only 64% in patients treated by angioplasty and stenting. But: indication for stenting was residual stenosis of > 50% after angioplasty Stenting at the costoclavicular junction without surgical decompression is not advised due to high rate of stent fractures and reocclusions Lee WA, et al. J Vasc Surg. 2000;32: Kreienberg PB, et al. J Vasc Surg. 2001;33(2 Suppl):S Lee JT, et al. J Vasc Surg. 2006;43: ConfirmedacuteUEDVT Ini5alan5coagula5on: a)for"proximal"uedvt:ufh,lmwh,orfondaparinuxforatleast5days(grade&1b);withlmwhorfondaparinuxoverivufh(grade2c)orscufh(grade2b) b)for"distal"uedvt:"clinicalorultrasoundsurveillancewithoutan$coagula$on,orprophylac$cdoseortherapeu$cdosean$coagula$on(favoran$coagula$onif catheter?associatedwithoutcatheterremoval,orincancerpa$entswithlowbleedingrisk) CatheterFdirectedthrombolysisorpharmacomechanicalthrombectomy ifseveresymptoms/signsofuedvtinvolvingmostofsubclavian/axillaryvein,withlowriskofbleedingandgoodfunc$onalstatus;otherwise an$coagula$onalone(grade2c) ForSVCsyndrome: Urgentangioplasty/stent ifseveresymptoms; Addi$onallyformalignantSVC syndrome:radiotherapy, chemotherapy,orsurgery dependingontumortypeand staging ForcatheterFassociatedUEDVT: Norou$neCVCremoval(Grade& 2C). Considercatheterremovalif: Cathetermalfunc$onor infec$on Contraindica$onto an$coagula$on Persistentsymptomsorsignsof UEDVTduringini$altreatment Catheternolongerneeded ForidiopathicUEVT: performcancerscreening Forvenousthoracicoutlet syndrome: Surgicaldecompression ±angioplasty/stent ifpersistentsymptomsofuedvt andvenousobstruc$onby conven$onalphlebographyaxer ini$altreatment Longterman5coagula5on(includesvitaminKantagonist,LMWH,dabigatranorrivaroxaban):"" a)for"proximal"uedvt:an$coagula$on 3months(Grade2B),ifnotassociatedwithCVCorcancerfor3months(Grade1B) catheter?associateduedvt:ifcvcwasremoved:an$coagula$onfor3months(grade1b,andgrade2bincancerpa$ents);ifcvcwasnotremoved: an$coagula$onaslongascvcremains(grade2c,andgrade1cincancerpa$ents) b)for"distal"uedvt:<3monthsifan$coagula$onischosen Engelberger RP & Kucher N: Circulation. 2012;126: