Use of novel antithrombotic agents for COVID‐19: Systematic summary of ongoing randomized controlled trials

Talasaz, Azita H.; Sadeghipour, Parham; Aghakouchakzadeh, Maryam; Kakavand, Hessam; Ariannejad, Hamid; Connors, Jean M.; Hunt, Beverley J.; Berger, Jeffrey S.; Tassell, Benjamin Van; Piazza, Gregory; Weitz, Jeffrey I.; Cushman, Mary; Lip, Gregory Y.H.; Goldhaber, Samuel Z.; Bikdeli, Behnood

doi:10.1111/jth.15533

Cited by 13 publications

(17 citation statements)

References 31 publications

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“…Regarding similar compounds that emerged from the prediction results of the three SAE-DNN models, these compounds were predicted to have interactions with COVID-19 proteins. This is supported by several literature studies showing that Hyperoside, Aloin, Rhamnetin, Laurotetanine, and Isoquercetin compounds have anti-inflammatory properties [52][53][54][56][57][58], which can help fight the hyper inflammation process in COVID-19 patients. For Garcimangosone d, its efficacy on COVID-19 or the inflammatory process in the body is not yet known.…”

Section: Herbal Compounds Predictionsupporting

confidence: 56%

Screening of Potential Indonesia Herbal Compounds Based on Multi-Label Classification for 2019 Coronavirus Disease

Fadli

Kusuma

Annisa

et al. 2021

BDCC

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Coronavirus disease 2019 pandemic spreads rapidly and requires an acceleration in the process of drug discovery. Drug repurposing can help accelerate the drug discovery process by identifying new efficacy for approved drugs, and it is considered an efficient and economical approach. Research in drug repurposing can be done by observing the interactions of drug compounds with protein related to a disease (DTI), then predicting the new drug-target interactions. This study conducted multilabel DTI prediction using the stack autoencoder-deep neural network (SAE-DNN) algorithm. Compound features were extracted using PubChem fingerprint, daylight fingerprint, MACCS fingerprint, and circular fingerprint. The results showed that the SAE-DNN model was able to predict DTI in COVID-19 cases with good performance. The SAE-DNN model with a circular fingerprint dataset produced the best average metrics with an accuracy of 0.831, recall of 0.918, precision of 0.888, and F-measure of 0.89. Herbal compounds prediction results using the SAE-DNN model with the circular, daylight, and PubChem fingerprint dataset resulted in 92, 65, and 79 herbal compounds contained in herbal plants in Indonesia respectively.

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Section: Herbal Compounds Predictionsupporting

confidence: 56%

Screening of Potential Indonesia Herbal Compounds Based on Multi-Label Classification for 2019 Coronavirus Disease

Fadli

Kusuma

Annisa

et al. 2021

BDCC

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“…Third, nafamostat show anticoagulant (AT) effects [42,44,82]. In fact, a number of clinical trials examining these issues are currently underway [83].…”

Section: Synthetic Protease Inhibitormentioning

confidence: 99%

Therapeutic Strategies for Disseminated Intravascular Coagulation Associated with Aortic Aneurysm

Yamada

Asakura

2022

IJMS

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Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both coagulation and fibrinolysis are markedly activated. Typical cases show decreased platelet counts and fibrinogen levels, increased concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer, and increased FDP/D-dimer ratios. Thrombin-antithrombin complex or prothrombin fragment 1 + 2, as markers of coagulation activation, and plasmin-α2 plasmin inhibitor complex, a marker of fibrinolytic activation, are all markedly increased. Prolongation of prothrombin time (PT) is not so obvious, and the activated partial thromboplastin time (APTT) is rather shortened in some cases. As a result, DIC can be neither diagnosed nor excluded based on PT and APTT alone. Many of the factors involved in coagulation and fibrinolysis activation are serine proteases. Treatment of enhanced-fibrinolytic-type DIC requires consideration of how to control the function of these serine proteases. The cornerstone of DIC treatment is treatment of the underlying pathology. However, in some cases surgery is either not possible or exacerbates the DIC associated with aortic aneurysm. In such cases, pharmacotherapy becomes even more important. Unfractionated heparin, other heparins, synthetic protease inhibitors, recombinant thrombomodulin, and direct oral anticoagulants (DOACs) are agents that inhibit serine proteases, and all are effective against DIC. Inhibition of activated coagulation factors by anticoagulants is key to the treatment of DIC. Among them, DOACs can be taken orally and is useful for outpatient treatment. Combination therapy of heparin and nafamostat allows fine-adjustment of anticoagulant and antifibrinolytic effects. While warfarin is an anticoagulant, this agent is ineffective in the treatment of DIC because it inhibits the production of coagulation factors as substrates without inhibiting activated coagulation factors. In addition, monotherapy using tranexamic acid in cases of enhanced-fibrinolytic-type DIC may induce fatal thrombosis. If tranexamic acid is needed for DIC, combination with anticoagulant therapy is of critical importance.

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“…Anticoagulant therapies that also have anti-inflammatory and antiviral effects, such as heparin and nafamostat, hold promise as treatments for COVID-19. Currently, a number of clinical trials investigating nafamostat for COVID-19 are underway [ 137 ].…”

Section: Covid-19-associated Coagulopathymentioning

confidence: 99%

Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination

Yamada

Asakura

2022

IJMS

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Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.

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Use of novel antithrombotic agents for COVID‐19: Systematic summary of ongoing randomized controlled trials

Cited by 13 publications

References 31 publications

Screening of Potential Indonesia Herbal Compounds Based on Multi-Label Classification for 2019 Coronavirus Disease

Screening of Potential Indonesia Herbal Compounds Based on Multi-Label Classification for 2019 Coronavirus Disease

Therapeutic Strategies for Disseminated Intravascular Coagulation Associated with Aortic Aneurysm

Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination

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