Prevention and treatment of the postthrombotic syndrome
2010; Elsevier BV; Volume: 52; Issue: 5 Linguagem: Inglês
10.1016/j.jvs.2010.05.070
ISSN1097-6809
Autores Tópico(s)Atrial Fibrillation Management and Outcomes
ResumoRecurrent ipsilateral deep venous thrombosis (DVT) is a primary and probably the most important etiologic factor in the development of the postthrombotic syndrome (PTS).1Prandoni P. Kahn S.R. Post-thrombotic syndrome: prevalence, prognostication and need for progress.Br J Haematol. 2009; 145: 286-295Crossref PubMed Scopus (184) Google Scholar, 2Prandoni P. Villalta S. Bagatella P. Rossi L. Marchiori A. Piccioli A. et al.The clinical course of deep-vein thrombosis Prospective long-term follow-up of 528 symptomatic patients.Haematologica. 1997; 82: 423-428PubMed Google Scholar Reducing the rate of recurrent DVT will thereby decrease the incidence of PTS. This can only be accomplished by modifying approaches to the current medical management of primary DVT. Furthermore, capitalizing on available strategies, such as patient and physician education, establishing hospital wide protocols for the prevention and treatment of DVT, and adherence to consensus guidelines, will help to optimize the treatment of DVT and thereby reduce the rate of recurrent DVT. The following issues are paramount to realizing a primary goal of recurrent DVT prevention (Table I): 1) identification of subgroups of patients who are at risk for recurrence, as DVT is heterogeneous with regard to anatomic extent, provoked by identified risk factors versus unprovoked, and cancer- versus non-cancer-related;3Agnelli G. Becattini C. Treatment of DVT: how long is enough and how do you predict recurrence?.J Thromb Thrombolysis. 2008; 25: 37-44Crossref PubMed Scopus (58) Google Scholar, 4Zhu T. Martinez I. Emmerich J. Venous thromboembolism: risk factors for recurrence.Arterioscler Thromb Vasc Biol. 2009; 29: 298-310Crossref PubMed Scopus (161) Google Scholar 2) optimizing the initiation, duration, and type of anticoagulation for each patient, including maintaining appropriate intensity of oral anticoagulation;5Siragusa S. Caramazza D. Malato A. How should we determine length of anticoagulation after proximal deep vein thrombosis of the lower limbs?.Br J Haematol. 2009; 144: 832-837Crossref PubMed Scopus (6) Google Scholar, 6Kearon C. Kahn S.R. Agnelli G. Goldhaber S. Raskob G.E. Comerota A.J. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest. 2008; 133 (8th Edition): 454S-545SCrossref PubMed Scopus (1842) Google Scholar, 7Streiff M.B. Segal J.B. Tamariz L.J. Jenckes M.W. Bolger D.T. Eng J. et al.Duration of vitamin K antagonist therapy for venous thromboembolism: a systematic review of the literature.Am J Hematol. 2006; 81: 684-691Crossref PubMed Scopus (14) Google Scholar 3) provision of anti-thrombotic prophylaxis to high risk medical and surgical patients;4Zhu T. Martinez I. Emmerich J. Venous thromboembolism: risk factors for recurrence.Arterioscler Thromb Vasc Biol. 2009; 29: 298-310Crossref PubMed Scopus (161) Google Scholar, 8Schulman S. Granqvist S. Holmström M. Carlsson A. Lindmarker P. Nicol P. et al.The duration of oral anticoagulant therapy after a second episode of venous thromboembolism The Duration of Anticoagulation Trial Study Group.N Engl J Med. 1997; 336: 393-398Crossref PubMed Scopus (603) Google Scholar, 9Trujillo-Santos J. Nieto J.A. Tiberio G. Piccioli A. Di Micco P. Prandoni P. Monreal M. RIETE RegistryPredicting recurrences or major bleeding in cancer patients with venous thromboembolism Findings from the RIETE Registry.Thromb Haemost. 2008; 100: 435-439Crossref PubMed Scopus (134) Google Scholar and 4) educating patients and front-line physicians regarding appropriate DVT management and risks of recurrent DVT.10Boddi M. Barbani F. Abbate R. Bonizzoli M. Batacchi S. Lucente E. et al.Reduction in deep vein thrombosis incidence in intensive care after a clinician education program.J Thromb Haemost. 2010; 8: 121-128Crossref PubMed Scopus (32) Google Scholar, 11Le Sage S. McGee M. Emed J.D. Knowledge of venous thromboembolism (VTE) prevention among hospitalized patients.J Vasc Nurs. 2008; 26: 109-117Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Preventing recurrent DVT will also reduce the incidence of pulmonary embolism (PE) and PE-associated mortality.12Tapson V.F. Acute pulmonary embolism.N Engl J Med. 2008; 358: 1037-1052Crossref PubMed Scopus (655) Google Scholar AC, Anticoagulation; ACCP, American College of Chest Physicians; LMWH, low-weight molecular heparin; PTS, postthrombotic syndrome; US, ultrasound; VKA, vitamin K antagonist. A number of studies have attempted to identify factors that could be used to risk stratify DVT patients with regard to risk of recurrence. Identification of residual venous thrombosis on ultrasound has been associated with an increased incidence of recurrent DVT, suggesting that an abnormal vein wall predisposes to recurrent thrombosis or that residual ‘thrombus’ represents an ongoing thrombosis-thrombolysis state.13Prandoni P. Lensing A.W. Prins M.H. Bernardi E. Marchiori A. Bagatella P. et al.Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism.Ann Intern Med. 2002; 137: 955-960Crossref PubMed Scopus (462) Google Scholar, 14Piovella F. Crippa L. Barone M. Viganò D'Angelo S. Serafini S. Galli L. et al.Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs: association with recurrence and new thrombosis.Haematologica. 2002; 87: 515-522PubMed Google Scholar, 15Siragusa S. Malato A. Anastasio R. Cigna V. Milio G. Amato C. et al.Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study.Blood. 2008; 112: 511-515Crossref PubMed Scopus (146) Google Scholar However, standard criteria or definitions to guide ultrasonographic characterization of residual venous thrombus are lacking. Furthermore, ultrasound diagnosis of residual venous thrombus is hampered by the wide variability in sonography technique between users and institutions. For example, there are no Intersocietal Commission for Accreditation of Vascular Laboratories guidelines for characterizing this finding. Some studies have reported that elevated D-dimer levels could be useful for predicting the risk of recurrent DVT, but this requires the patient being off anticoagulation for 1 month prior to determining whether to cease or continue therapy.16Cosmi B. Legnani C. Tosetto A. Pengo V. Ghirarduzzi A. Testa S. et al.Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study.Blood. 2010; 115: 481-488Crossref PubMed Scopus (116) Google Scholar, 17Palareti G. Cosmi B. Legnani C. Tosetto A. Brusi C. Iorio A. et al.D-dimer testing to determine the duration of anticoagulation therapy.N Engl J Med. 2006; 355: 1780-1789Crossref PubMed Scopus (560) Google Scholar It is unclear what the DVT risk is during this interval, although it is probably low.18McBane R.D. Wysokinski W.E. Daniels P.R. Litin S.C. Slusser J. Hodge D.O. et al.Periprocedural anticoagulation management of patients with venous thromboembolism.Arterioscler Thromb Vasc Biol. 2010; 30: 442-448Crossref PubMed Scopus (58) Google Scholar Moreover, while D-dimer is very sensitive, it is not specific and thus not as useful to ‘rule in’ a DVT. Thirdly, the use of other biomarkers to further stratify the risk of recurrence is an understudied area. Initial work has demonstrated a role for inflammatory markers such as P-selectin, ICAM-1, and IL-6 in DVT as well as PTS.19Shbaklo H. Holcroft C.A. Kahn S.R. Levels of inflammatory markers and the development of the post-thrombotic syndrome.Thromb Haemost. 2009; 101: 505-512PubMed Google Scholar, 20Barnes D.M. Wakefield T.W. Rectenwald J.E. Novel biomarkers associated with deep venous thrombosis: a comprehensive review.Biomark Insights. 2008; 3: 93-100PubMed Google Scholar Finally, it is equally important to determine who is at low risk for DVT recurrence as it is to determine those likely to recur.21Rodger M.A. Kahn S.R. Wells P.S. Anderson D.A. Chagnon I. Le Gal G. et al.Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.CMAJ. 2008; 179: 417-426Crossref PubMed Scopus (422) Google Scholar Two large studies suggest long-term vitamin K antagonist VKA use is safe for preventing recurrent DVT, but the duration and intensity varies.22Kearon C. Gent M. Hirsh J. Weitz J. Kovacs M.J. Anderson D.R. et al.A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.N Engl J Med. 1999; 340: 901-907Crossref PubMed Scopus (1053) Google Scholar, 23Ridker P.M. Goldhaber S.Z. Danielson E. Rosenberg Y. Eby C.S. Deitcher S.R. et al.PREVENT InvestigatorsLong-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.N Engl J Med. 2003; 348: 1425-1434Crossref PubMed Scopus (790) Google Scholar Such stratification could assist in management decisions as to the appropriate duration of anticoagulation so as to reduce the risk of bleeding inherent to all anticoagulants.24Eikelboom J.W. Quinlan D.J. O'Donnell M. Major bleeding, mortality, and efficacy of fondaparinux in venous thromboembolism prevention trials.Circulation. 2009; 120: 2006-2011Crossref PubMed Scopus (66) Google Scholar Finally, population data as to the rate of recurrent DVT, compared with rates of primary DVT, as well as identification of additional risk factors for unprovoked DVT, are needed. Practical measures to achieve a reduction in recurrent DVT include: promoting and disseminating best practice guidelines (eg, as are currently available in the American College of Chest Physicians [ACCP] guidelines);25Geerts W.H. Bergqvist D. Pineo G.F. Heit J.A. Samama C.M. Lassen M.R. Colwell C.W. American College of Chest PhysiciansPrevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest. 2008; 133 (8th Edition): 381S-453SCrossref PubMed Scopus (3540) Google Scholar to establish a new International Classification of Diseases, Revision 9 (ICD-9) code for recurrent DVT that can be used for nationwide administrative tracking; producing a patient education handout and widespread teaching web seminars on reducing the risk of recurrent DVT; and harnessing the electronic medical record to flag patients at high recurrence risk. The electronic medical record could be modified to automatically flag high risk patients (by key words in the medical record such as ‘iliofemoral DVT,' occluded common femoral vein, etc.). Realistically, this will have to occur at a local level. There is already high quality evidence that electronic reminders directed to physicians increase the use of thromboprophylaxis and also reduce the risk of primary DVT26Kucher N. Koo S. Quiroz R. Cooper J.M. Paterno M.D. Soukonnikov B. Goldhaber S.Z. Electronic alerts to prevent venous thromboembolism among hospitalized patients.N Engl J Med. 2005; 352: 969-977Crossref PubMed Scopus (735) Google Scholar; similar approaches could be tried to reduce the risk of recurrent DVT. Providing a ‘DVT information card’ to patients, to be given to their physician when admitted to the hospital, would assure that the health care team is aware of a patient's prior history of DVT. The new oral anticoagulants may lead to better compliance and safer, more uniform intensity of anticoagulation.27Gross P.L. Weitz J.I. New anticoagulants for treatment of venous thromboembolism.Arterioscler Thromb Vasc Biol. 2008; 28: 380-386Crossref PubMed Scopus (158) Google Scholar The measures to track success include following change in ICD-9, (ICD-10 Clinical Modification [CM]) codes, to propose a registry with anticoagulation and ultrasound use in patients with recurrent DVT, and to create a survey to assess adherence to current DVT treatment guidelines. Success will also be measured by whether we can achieve partnerships with industry to create and distribute DVT identification cards. These could be packaged with compression stockings and low-molecular weight heparin that are prescribed for the initial DVT. The best practice guideline would be interfaced with the Venous Disease Coalition meeting (VDC), September, 2010 with action plans for distribution. Educational materials could be created within 1 to 2 years. The registry, petition for ICD-10 code addition, and patient cards may take significantly longer to complete, depending on availability of funding. The effects of elastic compression stockings (ECS) following DVT have been well described, with such benefits as reduction in venous hypertension, decreased edema, and improvements in the tissue microcirculation.28Pierson S. Pierson D. Swallow R. Johnson Jr, G. Efficacy of graded elastic compression in the lower leg.JAMA. 1983; 249: 242-243Crossref PubMed Scopus (68) Google Scholar Furthermore, the effectiveness of ECS in the prevention of PTS has been demonstrated in prospective randomized trials.29Prandoni P. Lensing A.W. Prins M.H. Frulla M. Marchiori A. Bernardi E. et al.Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial.Ann Intern Med. 2004; 141: 249-256Crossref PubMed Scopus (568) Google Scholar, 30Brandjes D.P. Büller H.R. Heijboer H. Huisman M.V. de Rijk M. Jagt H. ten Cate J.W. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.Lancet. 1997; 349: 759-762Abstract Full Text Full Text PDF PubMed Scopus (818) Google Scholar Additionally, when ECS are combined with early ambulation, rates of PTS are decreased.31Partsch H. Blattler W. Compression and walking versus bed rest in the treatment of proximal deep venous thrombosis with low molecular weight heparin.J Vasc Surg. 2000; 32: 861-869Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar, 32Partsch H. Kaulich M. Mayer W. Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome.Int Angiol. 2004; 23: 206-212PubMed Google Scholar However, despite the well-documented benefit of early compression, the use of ECS is not universal, even amongst vascular specialists.33Kahn S.R. Elman E. Rodger M.A. Wells P.S. Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicians and patients.J Thromb Haemost. 2003; 1: 500-506Crossref PubMed Scopus (55) Google Scholar, 34Arpaia G. Cimminiello C. Mastrogiacomo O. de Gaudenzi E. Efficacy of elastic compression stockings used early or after resolution of the edema on recanalization after deep venous thrombosis: the COM.PRE Trial.Blood Coagul Fibrinolysis. 2007; 18: 131-137Crossref PubMed Scopus (37) Google Scholar Moreover, patient compliance is decreased by the difficulty of putting stockings on, discomfort, and cost.33Kahn S.R. Elman E. Rodger M.A. Wells P.S. Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicians and patients.J Thromb Haemost. 2003; 1: 500-506Crossref PubMed Scopus (55) Google Scholar The following issues are identified to improve the use of and compliance with compression and ambulation. First, there needs to be a consensus for standardization of the type of medical compression used, its time of initiation, and duration of use for acute DVT as well as PTS prevention and treatment. This includes incorporating the concept of immediate compression into the acute DVT treatment setting. For example, patients who are discharged from the emergency room should be prescribed either ECS or temporary elastic wraps as part of the treatment of acute DVT. This practice is consistent with current ACCP guidelines.35Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 338S-400SCrossref PubMed Scopus (2740) Google Scholar Second, establishing closer partnerships with the medical compression industry is necessary to encourage the development of more comfortable and user-friendly products, with the expectation that this will improve patient acceptance and compliance. In addition, direct communication between industry representatives and patients needs to be established so as to provide product support for patients who are experiencing difficulties using ECS. Product support could be offered in the clinic setting, by telephone, electronic mail, or on company websites. Important questions remain as to the true magnitude of effectiveness and general feasibility of using ECS to prevent PTS in patients with DVT.36Kahn S.R. How I treat postthrombotic syndrome.Blood. 2009; 114: 4624-4631Crossref PubMed Scopus (115) Google Scholar First, previous trials had various limitations that could affect their validity and generalizability, including modest sample size, recruitment at a single center, lack of placebo control, and lack of blinding of assessors. Although ECS are unlikely to cause harm, they are difficult to apply, uncomfortable, expensive, and require replacement every few months. It is unknown what the duration of ECS is that offers the prescribed amount of compression before wearing out. The SOX Trial, an ongoing large multi-center blinded trial that is comparing active versus placebo stockings to prevent PTS after proximal DVT, is anticipated to provide important additional information on the effectiveness of ECS.37Kahn S.R. Shbaklo H. Shapiro S. Wells P.S. Kovacs M.J. Rodger M.A. et al.Effectiveness of compression stockings to prevent the post-thrombotic syndrome (the SOX Trial and Bio-SOX biomarker substudy): a randomized controlled trial.BMC Cardiovasc Disord. 2007; 7: 21Crossref PubMed Scopus (58) Google Scholar Second, it is not definitively known whether ECS are effective in patients with symptomatic distal DVT, because the above-mentioned trials enrolled only patients with proximal DVT. Third, it is unclear whether ECS prevent PTS or merely palliate it, in which case it may be equally effective and more convenient for patients to initiate the use of ECS at the time of onset of PTS. Fourth, evaluation of the effectiveness of ECS with lighter (20-30 mm Hg) compression strength to prevent PTS is necessary, as these are easier to apply than are 30 to 40 mm Hg ECS, especially for older patients. Of note, these two levels of compression appear to have similar effectiveness in preventing recurrent venous ulcer.38Nelson E.A. Harper D.R. Prescott R.J. Gibson B. Brown D. Ruckley C.V. Prevention of recurrence of venous ulceration: randomized controlled trial of class 2 and class 3 elastic compression.J Vasc Surg. 2006; 44: 803-808Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar Finally, it is unknown for how long ECS need to be worn. Although the trials to date evaluated the use of ECS for 2 years or longer, a recent trial reported that beyond an initial 6-month period of use, there was no incremental benefit in prolonging compression therapy for an additional 18 months.39Aschwanden M. Jeanneret C. Koller M.T. Thalhammer C. Bucher H.C. Jaeger K.A. Effect of prolonged treatment with compression stockings to prevent post-thrombotic sequelae: a randomized controlled trial.J Vasc Surg. 2008; 47: 1015-1021Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar These observations suggest that the use of ECS for 6 months might be adequate, and would be easier for patients to tolerate than the currently recommended 2 years of use. Practical measures to achieve these objectives include increased contact with representatives of ECS companies, who would be encouraged to come to the physician's office and emergency rooms to disseminate compression and ambulation guidelines, and to increase research and development with the aim of improving compliance with compression. Patient education based in the emergency room or ambulatory setting is critical, as many patients with acute DVT are treated as outpatients. One measure of tracking success would be to determine stocking sales and distribution now, and again in 5 years time. While this is a surrogate for actual use, as a first step it would reflect ECS prescribing practices by physicians. Second, a focused emergency room (ER) physician survey on knowledge and practices with regard to ECS should be performed before and after focused education on the value of early ECS. Third, to specifically target the ER discharge information section of the chart, as well as the ER physicians, to ensure that patients are discharged with appropriate compression wrapping and stockings, in addition to their anticoagulants. Forth, another potential avenue to improving the use of compression after DVT may be to utilize the Veteran's Affairs medical centers and their electronic medical record and information technology systems to implement early pilot education and protocol programs for veterans in a consistent and captive patient population. Two areas that require further study include first, the use of dynamic pulse compression as adjunctive therapy for PTS; and second, developing the capability of embedding strength and stocking use microchip data within stockings. We anticipate that education and survey material could be distributed within 2 years, and a provider survey (listed above) analysis could be achieved in 5 years. We also anticipate partnering with the VDC to assist with the educational effort. The effective use of anticoagulation in DVT is known to reduce the risk of thrombus propagation, pulmonary embolism, and recurrent DVT. However, anticoagulation alone imperfectly protects against the occurrence of venous obstruction and valvular destruction, resulting in ambulatory venous hypertension and potentially PTS.40Shbaklo H. Kahn S.R. Long-term prognosis after deep venous thrombosis.Curr Opin Hematol. 2008; 15: 494-498Crossref PubMed Scopus (18) Google Scholar Some data suggests that prolonged low-molecular-weight heparin (LMWH) may be more effective than a VKA to promote vein recanalization and thereby reduce PTS.41Hull R.D. Pineo G.F. Brant R.F. Mah A.F. Burke N. Dear R. et al.Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer.Am J Med. 2006; 119: 1062-1072Abstract Full Text Full Text PDF PubMed Scopus (518) Google Scholar, 42Gonzalez-Fajardo J.A. Martin-Pedrosa M. Castrodeza J. Tamames S. Vaquero-Puerta C. Effect of the anticoagulant therapy in the incidence of post-thrombotic syndrome and recurrent thromboembolism: Comparative study of enoxaparin versus coumarin.J Vasc Surg. 2008; 48: 953-959Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Modest data suggest those with extensive DVT involving the iliofemoral segments are at excessive risk for postthrombotic morbidity.43Delis K.T. Bountouroglou D. Mansfield A.O. Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life.Ann Surg. 2004; 239: 118-126Crossref PubMed Scopus (279) Google Scholar, 44Kahn S.R. Shrier I. Julian J.A. Ducruet T. Arsenault L. Miron M.J. et al.Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis.Ann Intern Med. 2008; 149: 698-707Crossref PubMed Scopus (609) Google Scholar Early surgical thrombectomy and thrombus removal for iliofemoral DVT has been shown to decrease vein wall injury, preserve valve function, and ultimately decrease the occurrence of the PTS.45Plate G. Eklof B. Norgren L. Ohlin P. Dahlstrom J.A. Venous thrombectomy for iliofemoral vein thrombosis–10-year results of a prospective randomised study.Eur J Vasc Endovasc Surg. 1997; 14: 367-374Abstract Full Text PDF PubMed Scopus (198) Google Scholar, 46Comerota A.J. Gale S.S. Technique of contemporary iliofemoral and infrainguinal venous thrombectomy.J Vasc Surg. 2006; 43: 185-191Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Catheter-directed thrombolysis (CDT) has also been demonstrated in prospective randomized trials as an acceptable method of clot removal, with short term patency rates rivaling open thrombectomy.47Elsharawy M. Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis A randomised clinical trial.Eur J Vasc Endovasc Surg. 2002; 24: 209-214Abstract Full Text PDF PubMed Scopus (324) Google Scholar, 48Enden T. Kløw N.E. Sandvik L. Slagsvold C.E. Ghanima W. Hafsahl G. et al.Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency.J Thromb Haemost. 2009; 7: 1268-1275Crossref PubMed Scopus (220) Google Scholar Furthermore, CDT for the treatment of DVT results in improved quality of life when compared with anticoagulation alone, as well as decreased postthrombotic morbidity.49Comerota A.J. Catheter-directed thrombolysis for the treatment of acute iliofemoral deep venous thrombosis.Phlebology. 2001; 15: 149-155Crossref Scopus (66) Google Scholar, 50Grewal N. Martinez J. Andrews L. Comerota A.J. Successful thrombolysis of iliofemoral deep venous thrombosis reduces potthrombotic morbidity.Annual Meeting of the Midwestern Vascular Surgical Society. 2009; ([abstract])Google Scholar Thus, maximizing thrombus removal with catheter-based techniques is likely to be an important component to reducing PTS. In fact, it has been adopted by the 2008 ACCP guidelines, although is not a strong recommendation.6Kearon C. Kahn S.R. Agnelli G. Goldhaber S. Raskob G.E. Comerota A.J. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest. 2008; 133 (8th Edition): 454S-545SCrossref PubMed Scopus (1842) Google Scholar Despite the ACCP guidelines and two prospective randomized trials, much controversy surrounds the optimal use of early clot removal for the prevention of PTS, in part due to a lack of large, multicenter trials addressing the effectiveness and safety of this approach (Table II). The optimal timing of intervention and even the definition of “early thrombus removal” is unknown. Acute thrombus has been shown to respond better to thrombolysis than chronic organized DVT.51Strandness Jr, D.E. Langlois Y. Cramer M. Randlett A. Thiele B.L. Long-term sequelae of acute venous thrombosis.JAMA. 1983; 250: 1289-1292Crossref PubMed Scopus (332) Google Scholar Anecdotally and arbitrarily, CDT is used within a window of approximately 14 days. The use of catheter-based mechanical thrombectomy for thrombus resolution has also been well described.52Rao A.S. Konig G. Leers S.A. Cho J. Rhee R.Y. Makaroun M.S. Chaer R.A. Pharmacomechanical thrombectomy for iliofemoral deep vein thrombosis: an alternative in patients with contraindications to thrombolysis.J Vasc Surg. 2009; 50: 1092-1098Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar Combined pharmacomechanical lysis has the benefit of decreased treatment time, amount of thrombolytic used, cost, and hospital and intensive care unit stay.53Lin P.H. Zhou W. Dardik A. Mussa F. Kougias P. Hedayati N. et al.Catheter-direct thrombolysis versus pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis.Am J Surg. 2006; 192: 782-788Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar However, whether this benefit will translate into decreased rates of PTS is unknown. Currently, the most effective pharmacomechanical thrombolytic regimen is unknown, as there have been no head to head comparisons of the multiple devices and lytic agents.54McLafferty R.B. Endovascular management of deep venous thrombosis.Perspect Vasc Surg Endovasc Ther. 2008; 20: 87-91Crossref PubMed Scopus (21) Google Scholar, 55Gogalniceanu P. Johnston C.J. Khalid U. Holt P.J. Hincliffe R. Loftus I.M. Thompson M.M. Indications for thrombolysis in deep venous thrombosis.Eur J Vasc Endovasc Surg. 2009; 38: 192-198Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Furthermore, the role of venous stenting after lysis has not been established. It is unknown if routine stenting following lysis improves patency or whether stent use should be limited to selected cases with underlying anatomic or structural lesions. In addition, there are no venous flow criteria to determine who will benefit from surgical creation of an arteriovenous fistula. The clinical benefit and long-term outcome of aggressive thrombus removal in the femoral-popliteal segment is yet to be determined. Finally, the optimal surveillance of recurrence of thrombosis protocol after thrombus removal, choice of long-term anticoagulant, and the vein wall response after the procedure is completed requires study. An important area of future research is to assess new technology for removal of subacute clot (>14 days), and to more exactly define thrombus age using biomarkers. Practical measures to achieve these objectives are to ensure early referral of patients with iliofemoral and extensive thrombosis to venous specialists; and to establish a “red flag” notification system from the vascular laboratory when common femoral vein occlusion is detected, and alert the appropriate physicians. Further, to better promulgate an accepted anatomical classification system56Vedantham S. Valvular dysfunction and venous obstruction in the post-thrombotic syndrome.Thromb Res. 2009; 123: S62-S65Abstract Full Text PDF PubMed Scopus (41) Google Scholar for the location and extent of the thrombus, (such as iliofemoral vein involvement, instead of proximal vs distal vein). Education o
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