defibrotide and Blood-Coagulation-Disorders

Defibrotide (DF) is a polyribonucleotide with antithrombotic, pro-fibrinolytic, and anti-inflammatory effects on endothelium. These effects and the established safety of DF present DF as a strong candidate to treat viral and post-infectious syndromes involving endothelial dysfunction.. We discuss DF and other therapeutic agents that have the potential to target endothelial components of pathogenesis in viral and post-infectious syndromes. We introduce defibrotide (DF), describe its mechanisms of action, and explore its established pleiotropic effects on the endothelium. We describe the established pathophysiology of Coronavirus Disease 2019 (COVID-19) and highlight the processes specific to COVID-19 potentially modulated by DF. We also present influenza A and viral hemorrhagic fevers, especially those caused by hantavirus, Ebola virus, and dengue virus, as viral syndromes in which DF might serve therapeutic benefit. Finally, we offer our opinion on novel treatment strategies targeting endothelial dysfunction in viral infections and their severe manifestations.. Given the critical role of endothelial dysfunction in numerous infectious syndromes, in particular COVID-19, therapeutic pharmacology for these conditions should increasingly prioritize endothelial stabilization. Several agents with endothelial protective properties should be further studied as treatments for severe viral infections and vasculitides, especially where other therapeutic modalities have failed.

Topics: Blood Coagulation Disorders; COVID-19; Endothelium, Vascular; Humans; Polydeoxyribonucleotides; Post-Acute COVID-19 Syndrome; SARS-CoV-2

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; COVID-19; COVID-19 Drug Treatment; Humans; Polydeoxyribonucleotides

Topics: Blood Coagulation Disorders; COVID-19; Humans; Pandemics; Polydeoxyribonucleotides; SARS-CoV-2

Topics: Blood Coagulation Disorders; COVID-19; Fibrinolytic Agents; Humans; Pandemics; Polydeoxyribonucleotides; SARS-CoV-2

Sinusoidal obstructive syndrome (SOS) is a potentially fatal form of hepatic injury after hematopoietic stem cell transplantation. Patients can develop liver dysfunction, portal hypertension, ascites, coagulopathies, and multisystem organ failure. The mortality rate of severe SOS has been reported as high as 98% by day 100 after transplantation. Defibrotide, which is now approved for the treatment of SOS, has significantly decreased mortality. Defibrotide is a polynucleotide with profibrinolytic, anti-ischemic, and anti-inflammatory activity. These properties can increase the risk of life-threatening bleeding in this patient population. Previous protocols have suggested maintaining international normalized ratio ≤ 1.5, platelets > 30 k/uL, and fibrinogen ≥ 150 mg/dL to minimize this risk of bleeding. However, this can be challenging in fluid-sensitive patients with SOS. Thromboelastography (TEG) is a functional assay that evaluates the balance of procoagulant and anticoagulant proteins. In this series, TEG was used to guide defibrotide therapy as well as blood product transfusions in SOS patients with abnormal coagulation studies. Each patient recovered from SOS and had no bleeding complications. A randomized clinical trial is the next step in supporting the use of TEG in SOS patients with abnormal coagulation studies receiving defibrotide therapy.

Topics: Blood Coagulation Disorders; Child; Child, Preschool; Female; Fibrinolytic Agents; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Infant; Male; Platelet Aggregation Inhibitors; Polydeoxyribonucleotides; Thrombelastography