Goldhaber, Samuel Z

Kearon, Clive

Vedantham, Suresh

English

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Washington University School of MedicineDigital Commons@BeckerOpen Access Publications2018Pharmacomechanical therapy for deep-veinthrombosisSuresh VedanthamWashington University School of Medicine in St. LouisSamuel Z. GoldhaberHarvard Medical SchoolClive KearonMcMaster UniversityFollow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubsThis Letter is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications byan authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationVedantham, Suresh; Goldhaber, Samuel Z.; and Kearon, Clive, ,"Pharmacomechanical therapy for deep-vein thrombosis." The NewEngland Journal of Medicine.378,18. 1752-1753. (2018).https://digitalcommons.wustl.edu/open_access_pubs/7098Th e  n e w  e ngl a nd  j o u r na l  o f  m e dic i n en engl j med 378;18 nejm.org May 3, 201817521. Boubred F, Daniel L, Buffat C, et al. The magnitude of neph-ron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat: a comparative study in two experimental models. J Transl Med 2016; 14: 331.2. Lackland DT, Bendall HE, Osmond C, Egan BM, Barker DJ. Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med 2000; 160: 1472-6.3. Eriksson JG, Salonen MK, Kajantie E, Osmond C. Prenatal growth and CKD in older adults: longitudinal findings from the Helsinki Birth Cohort Study, 1924-1944. Am J Kidney Dis 2018; 71: 20-6.4. Vikse BE, Irgens LM, Leivestad T, Hallan S, Iversen BM. Low birth weight increases risk for end-stage renal disease. J Am Soc Nephrol 2008; 19: 151-7.5. Lentine KL, Kasiske BL, Levey AS, et al. KDIGO clinical prac-tice guideline on the evaluation and care of living kidney donors. Transplantation 2017; 101: Suppl 1: S1-S109.DOI: 10.1056/NEJMc1802894Pharmacomechanical Therapy for Deep-Vein ThrombosisTo the Editor: Regarding the recently published trial by Vedantham et al. (Dec. 7 issue),1 we wish to comment on the results that show an apparent lack of effectiveness of pharmacomechanical catheter-directed thrombolysis in preventing the post-thrombotic syndrome in patients with acute proximal deep-vein thrombosis. Only 58% of the patients had deep-vein thrombosis involving the iliac or common femoral veins, whereas 42% had femoral deep-vein thrombosis, which is as-sociated with a lower risk of the post-thrombotic syndrome.2 In addition, a high percentage of pa-tients (28%) received a venous stent (vs. 5.7% of the patients in the CAVENT [Catheter-Directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis] trial3). We wonder whether stent occlusion may have contributed to a higher inci-dence of the post-thrombotic syndrome in the pharmacomechanical-thrombolysis group than in the control group. Finally, various nonstandard-ized methods of pharmacomechanical catheter-directed thrombolysis were used, which makes interpretation difficult. Despite all these factors, the incidence of moderate-to-severe post-throm-botic syndrome was substantially lower in the pharmacomechanical-thrombolysis group than in the control group, and there were similar rates of major bleeding events at 24 months in the two groups. Given these issues, we believe that the outcomes of this trial are not generalizable. However, this trial does highlight the need for further studies with careful selection of patients and a more standardized approach.Sarju Ganatra, M.D. Ajay Sharma, M.D. Michael S. Levy, M.D.Lahey Hospital and Medical Center Burlington, MA sarju . ganatra@ lahey . orgNo potential conflict of interest relevant to this letter was re-ported.1. Vedantham S, Goldhaber SZ, Julian JA, et al. Pharmacome-chanical catheter-directed thrombolysis for deep-vein thrombo-sis. N Engl J Med 2017; 377: 2240-52.2. Kahn SR, Shrier I, Julian JA, et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008; 149: 698-707.3. Enden T, Haig Y, Kløw NE, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treat-ment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet 2012; 379: 31-8.DOI: 10.1056/NEJMc1802596The authors reply: Patients with femoral deep-vein thrombosis were included in our trial be-cause they also are at high risk for the post-thrombotic syndrome (which occurred in our trial in 44% of the patients with femoral deep-vein thrombosis vs. 50% of those with iliofemo-ral deep-vein thrombosis).1 Even in patients with iliofemoral deep-vein thrombosis, pharmacome-chanical thrombolysis did not prevent the post-thrombotic syndrome (which occurred in 49% of the patients with iliofemoral deep-vein throm-bosis in the pharmacomechanical-thrombolysis group and in 51% of those in the control group). However, pharmacomechanical thrombolysis re-sulted in a lower rate of moderate-to-severe post-thrombotic syndrome and in less severity of the symptoms and signs of the post-thrombotic syn-drome than was observed in the control group. These benefits appeared to be confined to pa-tients with iliofemoral deep-vein thrombosis.The thrombolytic methods used in this trial were standardized and reflected contemporary practice in the United States.2 All the operators were credentialed, and there were rigorous re-quirements for thrombolytic-drug administration and device use. Per accepted practice, stenting of residual iliac-vein lesions causing a reduction The New England Journal of Medicine Downloaded from nejm.org at Washington University in St. Louis Becker Library on September 24, 2018. For personal use only. No other uses without permission.  Copyright © 2018 Massachusetts Medical Society. All rights reserved. Correspondencen engl j med 378;18 nejm.org May 3, 2018 1753of more than 50% in the vein diameter, a pres-sure gradient of more than 2 mm Hg, or robust collateral filling was encouraged.3,4 In the ab-sence of a convincingly higher rate of recurrent deep-vein thrombosis in the pharmacomechanical-thrombolysis group than in the control group, it is unlikely that stent thrombosis was an im-portant contributor to the post-thrombotic syn-drome. The broad inclusion criteria, contempo-rary thrombolytic methods, and accommodation of physician expertise that were used in our trial support the generalizability of its results.Suresh Vedantham, M.D.Washington University in St. Louis St. Louis, MO vedanthams@ wustl . eduSamuel Z. Goldhaber, M.D.Harvard Medical School Boston, MAClive Kearon, M.B., Ph.D.McMaster University Hamilton, ON, CanadaSince publication of their article, the authors report no fur-ther potential conflict of interest.1. Kahn SR, Shrier I, Julian JA, et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008; 149: 698-707.2. Vedantham S, Goldhaber SZ, Kahn SR, et al. Rationale and design of the ATTRACT Study: a multicenter randomized trial to evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of postthrombotic syndrome in patients with prox-imal deep vein thrombosis. Am Heart J 2013; 165(4): 523-530.e3.3. Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hyper-tension: a scientific statement from the American Heart Asso-ciation. Circulation 2011; 123: 1788-830.4. Vedantham S, Sista AK, Klein SJ, et al. Quality improvement guidelines for the treatment of lower-extremity deep vein throm-bosis with use of endovascular thrombus removal. J Vasc Interv Radiol 2014; 25: 1317-25.DOI: 10.1056/NEJMc1802596Pleural DiseaseTo the Editor: With regard to the article by Feller-Kopman and Light (Feb. 22 issue),1 the dis-tinction between spontaneous pneumothorax that occurs in apparently healthy persons and pneu-mothorax caused by preexisting pulmonary dis-ease may seem arbitrary in terms of treatment, but an important aspect of the management of this condition is an evaluation for genetic dis-orders.A total of 10% of patients with spontaneous pneumothorax have a family history of pneumo-thorax.2 Heterozygous mutations in the tumor-suppressor gene FLCN predispose to the Birt–Hogg–Dubé syndrome, which is the most common genetic disorder in persons with fa-milial pneumothorax. This syndrome, which is identified in 10 to 15% of persons with familial pneumothorax, is associated with renal cancer.3 Spontaneous pneumothorax is also a complica-tion of certain genetic disorders that affect the integrity of connective tissue, transforming growth factor β signaling, or both. These dis-orders include Marfan’s syndrome, the Loeys–Dietz syndrome, vascular Ehlers–Danlos syn-drome, and homocystinuria. Moreover, inhibition of mechanistic target of rapamycin (mTOR) is a therapeutic target for pulmonary disease in tuber-ous sclerosis and lymphangioleiomyomatosis.4The identification of a genetic disorder that predisposes to pneumothorax is valuable in guid-ing surveillance for life-threatening extratho-racic manifestations and in counseling at-risk family members. Identification of molecular mechanisms presents possible therapeutic targets.Houriya Ayoubieh, M.D. Eyas Alkhalili, M.DJohns Hopkins University Baltimore, MDNo potential conflict of interest relevant to this letter was re-ported.1. Feller-Kopman D, Light R. Pleural disease. N Engl J Med 2018; 378: 740-51.2. Abolnik IZ, Lossos IS, Zlotogora J, Brauer R. On the inheri-tance of primary spontaneous pneumothorax. Am J Med Genet 1991; 40: 155-8.3. Scott RM, Henske EP, Raby B, Boone PM, Rusk RA, Marciniak SJ. Familial pneumothorax: towards precision medicine. Thorax 2018; 73: 270-6.4. McCormack FX, Inoue Y, Moss J, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med 2011; 364: 1595-606.DOI: 10.1056/NEJMc1803858To the Editor: Feller-Kopman and Light did not mention two possible therapeutic options for re-fractory hepatic hydrothorax. These options are placement of a transjugular intrahepatic porto-systemic shunt (TIPS) and liver transplantation.The use of a TIPS has been investigated in a number of uncontrolled studies and several case The New England Journal of Medicine Downloaded from nejm.org at Washington University in St. Louis Becker Library on September 24, 2018. For personal use only. No other uses without permission.  Copyright © 2018 Massachusetts Medical Society. All rights reserved. 

Pharmacomechanical therapy for deep-vein thrombosis

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Pharmacomechanical therapy for deep-vein thrombosis

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