ritonavir and Thrombophilia

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.

Topics: Adenosine Monophosphate; Alanine; Ambulatory Care; Antibodies, Antiphospholipid; Antibodies, Monoclonal, Humanized; Anticoagulants; Antirheumatic Agents; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Dose-Response Relationship, Drug; Drug Combinations; Duration of Therapy; Glucocorticoids; Hospitalization; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Ritonavir; SARS-CoV-2; Thrombolytic Therapy; Thrombophilia; Thrombosis; Venous Thromboembolism

In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.

Topics: Adenosine Monophosphate; Alanine; Anticoagulants; Antiviral Agents; Biomarkers; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Disease Management; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Embolism; Endothelium, Vascular; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Interferon beta-1b; Lopinavir; Macrophage Activation; Pandemics; Pneumonia, Viral; Pulmonary Fibrosis; Randomized Controlled Trials as Topic; Ritonavir; Thromboembolism; Thrombophilia; Thrombosis