Date of Completion
Spring 5-6-2022
Thesis Advisor(s)
Xiabo Zhong
Honors Major
Physiology and Neurobiology
Abstract
Hepatic Veno-Occlusive disease (Hepatic VOD) is a rare complication that can develop in patients following hematopoietic stem cell transplantation and high-dose chemotherapy. It is characterized by hepatomegaly, right upper quadrant pain, ascites, and jaundice [1,9]. The pathophysiology of hepatic VOD is not well understood but is generally understood as a cascade of events that begin with endothelial cell damage which leads to fibrosis and coagulation within hepatic vasculature. This rare condition can be treated with a drug called defibrotide sodium (sold under the name “Defitelio”). Defibrotide sodium is an antisense oligonucleotide (ASO) drug that promotes fibrinolysis (the breakdown of fibrin in blood vessels) via alteration of the enzymatic activity of plasmin. ASOs are a relatively new class of drugs that show great promise in treating various diseases and conditions. By studying the absorption, distribution, metabolism, and excretion (ADME) properties of ASOs, researchers can further improve of this cutting-edge therapy. A closer study of Defibrotide sodium, an approved ASO, allows for a better understanding of the potential of ASOs and a better familiarity with their mechanism.
In this paper, the clinical overview of hepatic VOD will be discussed, as well as the pathophysiology and clinical presentation of the rare condition. The mechanism of action and pharmacology of defibrotide sodium will be explored to better understand how it can be used to treat patients with hepatic VOD. In conjunction, the mechanisms of toxicity and adverse drug reactions will also be discussed in this paper. Finally, insight into the current knowledge gaps and the future of ASOs will be provided in this paper. By studying the clinical overview of Hepatic VOD and the characteristics of Defibrotide sodium, a better understanding as to the cutting-edge promise and potential of ASOs will be established.
Recommended Citation
Parikh, Rajvi J., "Spotlight on Defibrotide Sodium as a Treatment Option for Patients with Hepatic Veno-Occlusive Disease: Design, Development, and Place in Therapy, A Literature Review" (2022). Honors Scholar Theses. 1146.
https://digitalcommons.lib.uconn.edu/srhonors_theses/1146