Tomasa-Irriguible et al. Critical Care (2020) 24:325 https://doi.org/10.1186/s13054-020-03058-3 RESEARCH LETTER Open Access Low molecular weight heparins in COVID- 19 patients: beware of augmented renal clearance! Teresa Maria Tomasa-Irriguible1*, Sergi Martínez-Vega1, Ester Mor-Marco1, Alba Herraiz-Ruiz1, Laura Raguer-Pardo1 and Carlos Cubells-Larrosa2 Progressive respiratory failure is the primary cause of infrarenal inferior cava and the ipsilateral iliac, thus a death in the coronavirus disease 2019 pandemic (COVID- vena cava inferior filter was implanted. 19). Histologic analysis of pulmonary vessels in patients Afterwards, the administered deep vein thrombosis with COVID-19 has shown widespread thrombosis with prophylaxis (DVTP) regimen was reviewed. He had re- alveolar capillary microthrombi [1]. COVID-19 is known ceived enoxaparin 60 mg daily since admission. Hospital to be associated with thrombotic phenomena that are re- protocol advises 40 mg for patients below 80 kg and 60 lated to the high mortality of this disease and proper treat- mg for patients above 80 kg. The patient weighed 80 kg, ment can improve the survival of these patients [2–5]. so he was given the dose he was supposed to receive. Augmented renal clearance (ARC) is a phenomenon The renal function of the patient was also reviewed. He that frequently occurs in critically ill patients and can always had a glomerular filtration rate (GFR) above 90 cause therapeutic failure of renal removal drugs [6]. mL/min/1.73 m2, estimated by the Chronic Kidney Dis- Here is presented a clinical case to illustrate the topic. ease Epidemiology Collaboration (CKD-EPI) formula. A 52-year-old man without drug allergies or toxic habits, Nevertheless, once a week in ICU, we collect 24-h urine, with a history of dyslipidemia and obesity (BMI 32), was so as to be able to calculate the real GFR, and we found admitted to the hospital on 19 April with bilateral that he had ARC of up to 196 mL/min/1.73 m2 on hos- COVID-19 pneumonia. D-dimer value was 422 ng/mL at pital day 10. ICU admission. He needed 3 sessions of prone position Is it possible that the prophylactic dose of enoxaparin with a good response, so that on hospital day 12, intub- 60 mg daily was insufficient to prevent deep vein throm- ation was removed. On hospital day 14, he was dis- bosis (DVT) in this patient with COVID-19 plus ARC? charged from the ICU to the ward. However, that Is it also possible that a two-fold increase in the GFR afternoon, in the context of postural change, he devel- may also double enoxaparin removal? If so, could the oped oxygen desaturation at 55% with chest pain. D- same thing have happened to others? And what about dimer was 30,000 ng/mL. Electrocardiogram showed the therapeutic anticoagulant dosage? sinus tachycardia 130 bpm with typical S1Q3T3. An Subsequently, we analyzed the incidence of ARC in echocardiogram showed severe right cavity dysfunction, ICU patients during the COVID-19 pandemic. Of the 47 suggesting pulmonary thromboembolism (PE). An ar- patients admitted to the ICU for COVID-19, 18 (38.3%) teriography was performed confirming the suspicion and had ARC. Compared to non-ARC’s, both DVT and PE mechanical thrombectomy was performed. Cavography were higher in ARC (44% vs. 31%) and (33% vs. 10%, was also performed observing parietal thrombus in the P = 0.025), respectively. We also analyzed 2 patients with DVT plus ARC who were receiving 150 mg daily of * Correspondence: teresatomasa@gmail.com; enoxaparin (1.5 mg/kg/day) and the antiXa activity was ttomasa.germanstrias@gencat.cat 0.27 and 0.28 UI/mL, respectively, when the effective 1 Intensive Care Medicine Department, Germans Trias i Pujol Hospital, Carretera del Canyet s/n, 08916 Badalona, Barcelona, Spain range comprises 0.4–1.1 UI/mL. Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Tomasa-Irriguible et al. Critical Care (2020) 24:325 Page 2 of 2 Regarding the COVID-19 pandemic and the need of Publisher’s Note anticoagulants for DVTP, physicians have to be aware of Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. this ARC phenomenon and the risk of under exposure to low molecular weight heparins. This letter is to alert physicians as to the high incidence of ARC in these pa- tients and provide warning regarding the fact that regu- lar doses of low molecular weight heparin might not be protective enough for DVT and PE in this type of COVID-19 patient. Abbreviations ARC: Augmented renal clearance; BMI: Body mass index; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration formula; COVID-19: Coronavirus disease 2019 pandemic; DVT: Deep vein thrombosis; DVTP: Deep vein thrombosis prophylaxis; GFR: Glomerular filtration rate; ICU: Intensive care unit; PE: Pulmonary thromboembolism Acknowledgements We would like to sincerely thank all the healthcare personnel that worked awfully hard under the pressure of this pandemic. Authors’ contributions All authors discussed the content. TMT wrote a draft. SMV, EMM, AH, LR, and CC critically read and suggested changes. All authors read and approved the final version. Funding None Availability of data and materials Not applicable Ethics approval and consent to participate Not applicable Consent for publication Not applicable Competing interests None Author details 1 Intensive Care Medicine Department, Germans Trias i Pujol Hospital, Carretera del Canyet s/n, 08916 Badalona, Barcelona, Spain. 2Anesthesiology Department, Germans Trias i Pujol Hospital, Badalona, Barcelona, Spain. Received: 27 May 2020 Accepted: 3 June 2020 References 1. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19 [published online ahead of print, 2020 May 21]. N Engl J Med. 2020;https://doi.org/10.1056/ NEJMoa2015432. doi:10.1056/NEJMoa2015432. 2. Paranjpe I, Fuster V, Lala A, Russak A, Glicksberg BS, Levin MA, Charney AW, Narula J, Fayad ZA, Bagiella E, Zhao S, Nadkarni GN. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol. 2020. https://doi.org/10.1016/j. jacc.2020.05.001. 3. Lillicrap D. Disseminated intravascular coagulation in patients with 2019- nCoV pneumonia. J Thromb Haemost. 2020;18(4):786-7. 4. Yin S, Huang M, Li D, Tang N. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. J Thromb Thrombolysis. 2020;18(4):786-7. 5. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(4):786-7. 6. Tomasa Irriguible TM. Augmented renal clearance: much more is better? Med Int. 2018;42(8):500–3. https://doi.org/10.1016/j.medin.2018.02.004.