Thrombin Inhibition by Argatroban: Potential Therapeutic Benefits in COVID-19

Aliter, Kholoud F.; Al‐Horani, Rami A.

doi:10.1007/s10557-020-07066-x

Cited by 43 publications

(43 citation statements)

References 103 publications

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“…The largest study on thromboembolism during vvECMO therapy to date reports incidences of any type of thrombosis of 62% [ 4 ], and the fraction of 28% clinically significant thromboembolic events was comparable to that of the Argatroban group in this study. Eventually, Argatroban may be an alternative in cohorts with a high risk for thromboembolism such as COVID-19 patients [ 31 ] due to its antithrombotic action, presumably also working in already formed clots, and its potential anti-inflammatory, and theoretical antiviral characteristics [ 32 ]. Technical complications related to clotting were similar.…”

Section: Discussionmentioning

confidence: 99%

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Fisser¹,

Winkler²,

Malfertheiner³

et al. 2021

Crit Care

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Background During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. Methods We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). Results Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). Conclusion In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

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Section: Discussionmentioning

confidence: 99%

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Fisser¹,

Winkler²,

Malfertheiner³

et al. 2021

Crit Care

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“…Likewise, the Trovafloxacin drug, which is a broad-spectrum antibiotic, has been predicted to be an efficient Main protease (M pro ) inhibitor in a docking study done by Gimeno A, et al [38] . The Argatroban drug, which was earlier used as a thrombin inhibitor also shows promising inhibition against SARS-CoV-2 [39] . The Reboxetine drug, which was initially used to treat clinical depression, shows promising results in the in vitro study with ΔG binding (kcal/mol) of -8.86 and inhibiting M Pro [40] .…”

Section: Discussionmentioning

confidence: 99%

Prediction of repurposed drugs for Coronaviruses using artificial intelligence and machine learning

Rajput

Thakur

Mukhopadhyay

et al. 2021

Computational and Structural Biotechnology Journal

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“…has a short half-life (39-51 min in normal hepatic function) and can be discontinued quickly if needed. 12 In addition to argatroban, this patient also received IVIG. These treatments were targeted toward an autoimmunemediated, spontaneous HIT.…”

Section: Case Reportmentioning

confidence: 99%

“…Argatroban also has a short half-life (39–51 min in normal hepatic function) and can be discontinued quickly if needed. 12 …”

Section: Treatmentmentioning

confidence: 99%

Autoimmune heparin-induced thrombocytopenia: a rare manifestation of COVID-19

2021

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We describe the case of a 65-year-old male who presented to an outside hospital for shortness of breath, nausea and vomiting 8 days after testing positive for COVID-19. Initial workup revealed massive bilateral pulmonary emboli and thrombocytopenia. The patient was then admitted to our hospital, received an inferior vena cava filter and initially started on argatroban for autoimmune heparin-induced thrombocytopenia (HIT) prophylaxis. On hospital stay day 6, labs revealed a diagnosis of HIT in the setting of COVID-19. This case highlights the rare occurrence of a patient developing HIT without heparin exposure and in the setting of a novel infectious agent, COVID-19.

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Thrombin Inhibition by Argatroban: Potential Therapeutic Benefits in COVID-19

Cited by 43 publications

References 103 publications

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Prediction of repurposed drugs for Coronaviruses using artificial intelligence and machine learning

Autoimmune heparin-induced thrombocytopenia: a rare manifestation of COVID-19

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