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      N‐Methyl‐3,4‐methylendioxymethamphetamine (MDMA)‐related coagulopathy and rhabdomyolysis: A case series and literature review

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          Abstract

          Coagulation changes, thrombosis, and hemorrhage have been described in patients following N‐methyl‐3,4‐methylenedioxymethylamphetamine (MDMA) intoxication who subsequently developed serotonin syndrome and rhabdomyolysis. The clinical features and mechanism of this remain poorly described. We describe 5 sequential cases admitted to critical care due to severe recreational MDMA toxicity where coagulopathy occurred, and discuss key clinical issues. All patients presented with hyperpyrexia then developed subsequent rhabdomyolysis accompanied by a coagulopathy within 24 hours of presentation. This included a severe thrombocytopenia, prolonged coagulation times, grossly elevated D‐dimer levels, and hypofibrogenemia. Multiorgan dysfunction was seen in all patients, including stroke in one patient and major hemorrhage in another. In 2 cases, low‐dose low‐molecular‐weight heparin was used early after presentation, with no significant bleeding complications. Blood products usage was high but variable between the patients with lower use in those who received low‐molecular‐weight heparin early. Other treatments included intravascular therapeutic cooling, renal replacement therapy with large filter pores and cyprohepatidine. Current evidence suggests that in this group, rhabdomyolysis with subsequent myosin release may be a profound activator of coagulation leading to disseminated intravascular coagulation. Myosin‐activated coagulation seems a potential cause of MDMA‐related coagulopathy in the setting of rhabdomyolysis and serotonin syndrome. Further studies are needed to validate this and explore the use of low‐molecular‐weight heparin to reduce the clinical effects of this coagulopathy.

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          Most cited references23

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          Toxicity and deaths from 3,4-methylenedioxymethamphetamine ("ecstasy")

          The risk of adverse reactions to 3,4-methylenedioxymethamphetamine (MDMA), more commonly known as "ecstasy", is now widely known in both the USA and UK, but the patterns of illness remain varied. We report our experience during 1990 and 1991. There has been a recent increase in cases of severe toxicity following recreational misuse of small amounts of MDMA. Among 7 fatalities, the pattern of toxicity included fulminant hyperthermia, convulsions, disseminated intravascular coagulation, rhabdomyolysis, and acute renal failure. Until now, there have been few reports of this type of toxicity from MDMA, which may be related both to the potential of the drug to alter thermoregulation and to the circumstances of misuse. In addition, we have monitored 7 cases of hepatotoxicity and suspect that the frequency of this complication is increasing; a history of MDMA misuse should be sought in young people presenting with unexplained jaundice or hepatomegaly. We also describe 5 subjects involved in road traffic accidents in whom MDMA was identified. Misuse of MDMA can have severe acute toxic effects; few data are available concerning long-term morbidity, and this deserves close monitoring in future.
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            Evidence for endothelial cell activation/injury in heatstroke.

            We treated the hypothesis that heatstroke is associated with endothelial cell activation/injury and examined the possibility that the markers of endothelial cell activation/injury may be associated with its severity and complications such as disseminated intravascular coagulation, lung injury, and renal dysfunction. Prospective analyses. Heatstroke Center in Makkah, Saudi Arabia. Twenty-two adult patients with heatstroke. The plasma concentration of endothelin, circulating intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor-antigen values were measured, respectively, by radioimmunoassay, enzyme-linked immunosorbent assay, and rocket electroimmunoassay, in heatstroke patients on admission (precooling) and after complete cooling (postcooling), and in ten normal control patients. Precooling heatstroke patients (rectal temperature 40.9 +/- 1.1 [SD] degrees C) had increased circulating concentrations of endothelin, c-ICAM-1, and von Willebrand factor-antigen in 100%, 80%, and 77% of patients to 126.4 +/- 11.2 pmol/L, 523.1 +/- 154.4 ng/mL, and 3.85 +/- 2.3 U/mL, respectively (control values: 13.7 +/- 4.2 pmol/L [p .05). Our findings of increased circulating concentrations of circulating ICAM-1, endothelin, and von Willebrand factor-antigen are consistent with the hypothesis that heatstroke is associated with endothelial cell activation/injury. Whether the endothelial cell activation/injury is implicated in the pathophysiology of this disorder merits further studies.
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              High Cut-Off Renal Replacement Therapy for Removal of Myoglobin in Severe Rhabdomyolysis and Acute Kidney Injury: A Case Series

              Background/Aim: Rhabdomyolysis is associated with the release of myoglobin into the circulation, promoting acute kidney injury (AKI). In severe rhabdomyolysis, dialysis-dependent AKI doubles mortality. Standard blood purification techniques have limited efficacy in removing myoglobin. We describe high cut-off (HCO) renal replacement therapy (RRT) as a novel approach for extracorporeal elimination of myoglobin in rhabdomyolysis-associated AKI. Methods: With an in vivo molecular cut-off at 45 kDa, HCO filters are effective in removing myoglobin (17.8 kDa). Clearances across standard and HCO filters using continuous or intermittent RRT are reviewed in a case series of 11 patients with severe rhabdomyolysis and dialysis-dependent AKI. Results: Median myoglobin clearance across standard high-flux filters was 3.3 (interquartile range 2.3–3.9) ml/min for sustained low-efficiency daily dialysis (SLEDD) batch hemodialysis (HD) and 3.7 (2.9–6.7) ml/min for conventional HD. Respective clearances using HCO filters (membrane surface area: 1.1 m 2 ) were 21.7 (20.3–26.1) ml/min (SLEDD) and 44.2 (41.3–47.0) ml/min (HD). Corrected for filter size, up to 20-fold higher clearances were obtained using HCO filters, resulting in profound and sustained reduction of plasma myoglobin concentration. Conclusions: As a novel approach, HCO RRT allows for rapid and effective removal of myoglobin from the circulation. In light of the pathogenic role in AKI, reducing exposure of the kidney to myoglobin may improve renal recovery and patient outcome. Our data pave the way for prospective trials, addressing this issue.
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                Author and article information

                Contributors
                @doyley1_
                Beverley.Hunt@gstt.nhs.uk , @bhwords
                Journal
                Res Pract Thromb Haemost
                Res Pract Thromb Haemost
                10.1002/(ISSN)2475-0379
                RTH2
                Research and Practice in Thrombosis and Haemostasis
                John Wiley and Sons Inc. (Hoboken )
                2475-0379
                14 June 2020
                July 2020
                : 4
                : 5 ( doiID: 10.1002/rth2.v4.5 )
                : 829-834
                Affiliations
                [ 1 ] Centre for Thrombosis & Haemophilia St Thomas' Hospital London UK
                [ 2 ] Department of Intensive Care Medicine St Thomas' Hospital London UK
                Author notes
                [*] [* ] Correspondence

                Beverley J. Hunt, Centre for Thrombosis and Haemophilia, St Thomas' Hospital, London SE1 7EH, UK.

                Email: Beverley.Hunt@ 123456gstt.nhs.uk

                Author information
                https://orcid.org/0000-0002-1001-0486
                https://orcid.org/0000-0002-4709-0774
                Article
                RTH212360
                10.1002/rth2.12360
                7354411
                32685891
                42842469-1b83-42e7-884d-18c8d5a2be5e
                © 2020 The Authors. Research and Practice in Thrombosis and Haemostasis by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH)

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 30 December 2019
                : 03 April 2020
                : 10 April 2020
                Page count
                Figures: 0, Tables: 2, Pages: 6, Words: 3466
                Categories
                Case Report
                Original Articles: Hemostasis
                Custom metadata
                2.0
                July 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:12.07.2020

                3,4‐methylenedioxymethylamphetamine,coagulopathy,critical care,rhabdomyolysis,serotonin syndrome

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