Nafamostat mesylate-induced hyperkalemia in critically ill patients with COVID-19: Four case reports

Okajima, Masaki; Takahashi, Yūzō; Kaji, Takaaki; Ogawa, Naohiko; Mouri, Hisatsugu

doi:10.12998/wjcc.v8.i21.5320

Cited by 18 publications

(16 citation statements)

References 6 publications

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“…pancreatitis, has been shown as beneficial in COVID-19 treatment in several case reports. 45 Additional treatment may be required to decrease high levels of VWF antigen and activity and increase ADAMTS13 activity. A nanobody, caplacizumab, that inhibits the binding of VWF to gp-1b on platelets has been effective in treating TMAs.…”

Section: Discussionmentioning

confidence: 99%

Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients

Sweeney

Barouqa

Krause

et al. 2021

TH Open

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The causes of coagulopathy associated with coronavirus disease 2019 (COVID-19) are poorly understood. We aimed to investigate the relationship between von Willebrand factor (VWF) biomarkers, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with balanced distribution of survivors and nonsurvivors. Patients who died had significantly lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, significantly elevated lactate dehydrogenase levels, significantly increased shistocyte/RBC fragment counts, and significantly elevated VWF antigen and activity levels compared with patients discharged alive. These biomarkers correlate with markedly elevated D-dimers. Additionally, only 30% of patients who had an ADAMTS13 activity level of less than 43% on admission survived, yet 60% of patients survived who had an ADAMTS13 activity level of greater than 43% on admission. In conclusion, COVID-19 may present with low ADAMTS13 activity in a subset of hospitalized patients. Presence of schistocytes/RBC fragment and elevated D-dimer on admission may warrant a work-up for ADAMTS13 activity and VWF antigen and activity levels. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of treatments aimed at prevention and/or amelioration of microangiopathy in COVID-19.

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Section: Discussionmentioning

confidence: 99%

Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients

Sweeney

Barouqa

Krause

et al. 2021

TH Open

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“…In vitro Camostat and Nafamostat bind and inhibit TMPS2_HUMAN with great affinity, IC50 6.2 nM and 0.27 nM, respectively, but are not specific [ 44 ] and are not devoid of side effects in the patients [ 45 ]. In silico docking experiments have been carried out to find other inhibitors of TMPS2_HUMAN [ 46 ], but in vitro validation of the hits has not yet been carried out.…”

Section: Discussionmentioning

confidence: 99%

Protective Role of a TMPRSS2 Variant on Severe COVID-19 Outcome in Young Males and Elderly Women

Monticelli¹,

Mele

Benetti

et al. 2021

Genes

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The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients—young males and elderly women—and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity.

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“…Nafamostat mesylate is a serine protease inhibitor that blocks proteolytic enzymes, such as thrombin, plasmin, and trypsin, and has been used in Japan for disseminated intravascular coagulation and pancreatitis treatment [ 30 ]. In a small clinical case series study, Kent Doi et al found that the mortality rate in COVID-19 patients treated with combinations of nafamostat and favipiravir was low suggesting these combinations might be effective for critically ill patients due to this virus.…”

Section: Drug Re-purposing For Covid-19mentioning

confidence: 99%

“…On the other hand, a study conducted in Kanazawa University Hospital, Japan revealed that all COVID-19 patients developed hyperkalemia after receiving a course nafamostat therapy. This study warns monitoring serum potassium values closely after nafamostat initiation in COVID-19 patients to be compulsory [ 30 ].…”

Section: Drug Re-purposing For Covid-19mentioning

confidence: 99%

Roles of existing drug and drug targets for COVID-19 management

2021

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In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS–Cov, and SARS-Cov. Moreover, researchers are scrambling to identify novel drug targets and discover novel therapeutic options to vanquish the current pandemic. Since there is no definitive treatment to control Covid-19 vaccines are remain to be a lifeline. Currently, many vaccine candidates are being developed with most of them are reported to have positive results. Therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor-associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis were identified as a potential target against COVID-19 infection. This review also summarizes plant-based medicines for the treatment of COVID-19 such as saposhnikoviae divaricata, lonicerae japonicae flos, scutellaria baicalensis, lonicera japonicae, and some others. Thus, this review aimed to focus on the most promising therapeutic targets being repurposed against COVID-19 and viral elements that are used in COVID-19 vaccine candidates.

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Nafamostat mesylate-induced hyperkalemia in critically ill patients with COVID-19: Four case reports

Cited by 18 publications

References 6 publications

Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients

Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients

Protective Role of a TMPRSS2 Variant on Severe COVID-19 Outcome in Young Males and Elderly Women

Roles of existing drug and drug targets for COVID-19 management

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