Dynamic changes in fibrinogen and D-dimer levels in COVID-19 patients on nafamostat mesylate
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Dynamic changes in fibrinogen and D-dimer levels in COVID-19 patients on nafamostat mesylate Itsuki Osawa1 · Koh Okamoto1 · Mahoko Ikeda1,2 · Amato Otani1 · Yuji Wakimoto1 · Marie Yamashita1 · Takayuki Shinohara1 · Yoshiaki Kanno1 · Daisuke Jubishi1 · Makoto Kurano3 · Sohei Harada1,2 · Shu Okugawa1 · Yutaka Yatomi3 · Kyoji Moriya1,2 Accepted: 3 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Critical illnesses associated with coronavirus disease 2019 (COVID-19) are attributable to a hypercoagulable status. There is limited knowledge regarding the dynamic changes in coagulation factors among COVID-19 patients on nafamostat mesylate, a potential therapeutic anticoagulant for COVID-19. First, we retrospectively conducted a cluster analysis based on clinical characteristics on admission to identify latent subgroups among fifteen patients with COVID-19 on nafamostat mesylate at the University of Tokyo Hospital, Japan, between April 6 and May 31, 2020. Next, we delineated the characteristics of all patients as well as COVID-19-patient subgroups and compared dynamic changes in coagulation factors among each subgroup. The subsequent dynamic changes in fibrinogen and D-dimer levels were presented graphically. All COVID-19 patients were classified into three subgroups: clusters A, B, and C, representing low, intermediate, and high risk of poor outcomes, respectively. All patients were alive 30 days from symptom onset. No patient in cluster A required mechanical ventilation; however, all patients in cluster C required mechanical ventilation, and half of them were treated with venovenous extracorporeal membrane oxygenation. All patients in cluster A maintained low D-dimer levels, but some critical patients in clusters B and C showed dynamic changes in fibrinogen and D-dimer levels. Although the potential of nafamostat mesylate needs to be evaluated in randomized clinical trials, admission characteristics of patients with COVID-19 could predict subsequent coagulopathy. Keywords COVID-19 · Anticoagulant · D-dimer · Fibrinogen · Nafamostat mesylate
Highlights • All patients with COVID-19 treated on nafamostat
mesylate were alive at 30 days from symptom onset.
• Using cluster analysis based on clinical characteristics on
admission, we identified three subgroups among COVID19 patients with different clinical presentations of subsequent coagulopathy.
* Koh Okamoto kokamoto‑[email protected] 1
Department of Infectious Diseases, The University of Tokyo Hospital, 7‑3‑1 Hongo, Bunkyo‑ku, Tokyo 113‑0033, Japan
2
Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan
3
Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan
• Clinical characteristics on admission are beneficial in
predicting subsequent coagulopathy and consider individualized approaches for thromboembolism. • Since COVID-19-associated coagulopathy resembles DIC, a careful evaluation of dynamic changes in coagulopathy, as reflected by fibrino
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