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      Carotid Thromboembolism Associated with Nephrotic Syndrome Treated with Dabigatran

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          Abstract

          Nephrotic syndrome (NS) may be complicated by thromboembolism, which occasionally manifests as stroke. Although the optimal, standardized approach to the prophylaxis and management of thromboembolic complications associated with NS has not been established, anticoagulation with heparin and subsequent warfarin is the de facto standard of treatment. Dabigatran, a novel direct thrombin inhibitor, has become a substitute for warfarin and heparin for many indications, including the prophylaxis of stroke associated with nonvalvular atrial fibrillation and postoperative thromboprophylaxis in orthopedic patients. We report a 35-year-old male with NS due to membranous nephropathy (MN) that presented with carotid thromboembolism. Because the patient developed drug-induced hepatitis due to warfarin, we attempted treatment with dabigatran and were successful in continuing the medication without any complications. We also reviewed the literature on stroke associated with NS. Twenty-one prior cases have been reported, and the review of these cases revealed some interesting points. The age of onset ranged from 19 to 59 years. Most of the reported cases sustained a stroke at earlier ages than patients with atherosclerosis and atrial fibrillation, which suggests that NS may independently predispose individuals to arterial and venous thromboses. MN was the most common underlying pathology. Given that a standardized approach to the prophylaxis and management of thrombotic complications associated with NS has not been established, our experience suggests that dabigatran is a valid new treatment option for thrombotic complications of NS.

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          Most cited references 31

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          Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum.

          It has long been recognized that nephrotic syndrome is associated with an increased risk for thromboembolic complications, including deep venous thrombosis, renal vein thrombosis, and pulmonary embolism. This risk varies with the nature of the underlying disease and seems to be greatest for membranous nephropathy. Other factors, including the level of serum albumin, previous thromboembolic episodes, and a genetically determined predisposition to thrombosis, may also be involved. Prevention of thromboembolic events with oral anticoagulants in nephrotic syndrome requires a careful case-by-case analysis of the risks for thromboembolic events balanced by the risks for anticoagulant induced bleeding. Markov-based decision analysis using literature-based assumptions regarding these risks has suggested that prophylactic anticoagulants may be indicated in certain circumstances. Such decisions need to take into account the nature of the underlying disease, the severity of the nephrotic syndrome (as assessed by serum albumin concentration), preexisting thrombophilic states, and the overall likelihood of serious bleeding events consequent to oral anticoagulation (as assessed by the international normalized ratio for prothrombin time). The optimal duration of prophylactic anticoagulation is unknown but very likely extends to the duration of the nephrotic state per se.
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            Cerebral infarction in young men with nephrotic syndrome.

            Thrombosis is one of the main complications of nephrotic syndrome; however, cerebral infarction associated with nephrotic syndrome has been rarely reported. We describe acute cerebral infarction in two young men with nephrotic syndrome. Both had a hypercoagulable state based on hemostatic studies. By retrospectively reviewing the medical records of the past 10 years at our hospital, we found an additional five cases of cerebral infarction with nephrotic syndrome. Two of the patients were found to have nephrotic syndrome during admission for stroke. Hypercoagulability may be the major contributing factor of cerebral infarction in patients with nephrotic syndrome.
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              Arterial thrombosis in nephrotic syndrome.

              The nephrotic syndrome is characterized by profound changes in the turnover and concentration of most plasma proteins, including those involved in the coagulation pathways. Thromboembolic complications, especially venous, have been widely reported. Arterial thrombosis is a relatively rare complication and has been reported mainly in nephrotic children. In this report, an adult nephrotic patient who developed thromboses of his right middle cerebral and left femoral arteries is described. The patient died, and at postmortem no underlying arterial disease was found. Histology of the kidneys showed minimal change disease.
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                Author and article information

                Journal
                CRU
                CND
                10.1159/issn.2296-9705
                Case Reports in Nephrology and Dialysis
                S. Karger AG
                2296-9705
                2014
                January – April 2014
                21 March 2014
                : 4
                : 1
                : 42-52
                Affiliations
                Department of Nephrology, Okinawa Chubu Hospital, Okinawa, Japan
                Author notes
                *Yosuke Sasaki, MD, Okinawa Yaeyama Hospital, 732 Okawa, Ishigaki, Okinawa 907-0022 (Japan), E-Mail pqrstbb@yahoo.co.jp
                Article
                362162 PMC4000300 Case Rep Nephrol Urol 2014;4:42-52
                10.1159/000362162
                PMC4000300
                24803917
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 2, Pages: 11
                Categories
                Published: March 2014

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