Anticoagulation with argatroban in patients with acute antithrombin deficiency in severe COVID‐19

Potential ‘significance’ of monoclonal gammopathy of ‘undetermined significance’ during COVID-19 pandemic

“… IV Rituximab administration is prolonged, and needs hospital visits Maintenance Rituximab may either be omitted, or increased in frequency from 2-monthly to 3-monthly infusions $$$ Consider SC Rituximab wherever available to reduce hospital visits Autologous HSCT causes profound and prolonged immunosuppression [ 24 ] Both autologous HSCT, and renal transplant must be delayed for patients with MGRS, atleast till the COVID-19 pandemic is reasonably controlled Treatment of MGCS in patients with COVID-19 Immunosuppressive medications [ 19 ] PI, IMiDs, corticosteroids, DARA, alkylators, and Rituximab are potentially immunosuppressive Withhold all the immunosuppressive therapies at the first diagnosis of COVID-19 Resume treatment of MGCS later, once the patient recovers fully from COVID-19 General measures Risk of worsening cardiac, and renal function with COVID-19 in MGRS Treatment of MGCS must be supportive Meticulous monitoring of fluid, and electrolyte balance for MGRS patients Treatment of COVID-19 in patients with MGCS Anti-COVID-19 drugs [ 19 , 33 ] Remdesivir, Lopinavir/Ritonavir, Favipiravir, and dexamethasone have shown some efficacy Cardiotoxic- Remdesivir, Lopinavir/Ritonavir Nephrotoxic- Remdesivir These drugs may be cautiously used to treat COVID-19 in patients with MGCS as per national and institutional guidelines Remdesivir must not be used in MGRS patients with severe renal insufficiency, or on renal replacement therapy @ Tocilizumab [ 19 ] Could cause cardiovascular complications Use cautiously particularly for patients with MGRS Anti-coagulation Patients with AL amyloidosis have vascular friability, and haemostatic abnormalities which could predispose them to bleeding [ 19 ] LMWH is renally excreted [ 16 ] Reduced AT levels could reduce the efficacy of heparin [ 17 ]. Cautious use of anti-coagulant drugs in AL amyloidosis Renal modification of anticoagulant dose, and Anti-Xa activity-guided LMWH dosing for MGRS patients [ 16 …”

“…AT level-guided heparin dosing, or use of anticoagulant drugs with AT-independent mechanism of action (Argatroban, Dabigatran) [ 17 ]…”

“…Therefore, in such patients, physicians may have to consider increasing the heparin dose guided either by antithrombin levels, or coagulation indices like APTT for unfractionated heparin, and anti-Xa activity for low molecular weight heparin [ 16 ]. Alternate anticoagulants with antithrombin-independent mechanisms of action like directly acting anticoagulants (Argatroban, or possibly Dabigatran) could also be used [ 17 ].…”

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

“…Encouraging aspects also include the worldwide availability of the drug, its well-established pharmacokinetics and safety profiles, and the apparent lack of drug-drug interactions with potential anti-COVID-19 therapeutics under evaluation. In this direction, successful anticoagulation with argatroban was very recently reported in a small number of severely ill COVID-19 patients (N = 10) with acute antithrombin deficiency [101]. Nevertheless, the potential benefits of argatroban in COVID-19 patients remain largely hypothetical and will have to be clinically established via large, randomized, double-blinded, and controlled clinical trials.…”

Pharmacological treatment of COVID-19: an update

“…93 Argatroban, a direct thrombin inhibitor has been shown to improve thrombotic complications in COVID-19 patients who fail heparin therapy. 94 The role of other anticoagulants such as warfarin, dabigatran, bivalirudin, need to be investigated. Clinical trials are underway to study the effect of rivaroxaban and fondaparinux in COVID-19 patients with thrombotic complications.…”