BackgroundDefibrotide is a DNA-derived polyelectrolyte with anti-ischemic and antithrombotic effects, primarily used in post-bone marrow transplantation (BMT) veno-occlusive disease (VOD). Currently, it is produced from porcine mucosal tissue, which presents cultural, economic, and supply limitations.AimThis study compared coagulation activity, molecular profiles, and DNA content of porcine- versus ovine-derived defibrotide.MethodsActive pharmaceutical ingredient (API) samples of 19 porcine and 9 ovine defibrotide batches were dissolved in saline (1 mg/mL) and added to pooled plasma and whole blood (100 µg/mL). Coagulation was assessed using activated partial thromboplastin time (aPTT) and thrombin time (TT). Anti-Xa and anti-IIa activities were measured by amidolytic assays. DNA content was quantified via the heparin red method, and molecular weight was determined by size exclusion chromatography.ResultsNeither porcine nor ovine preparations showed anticoagulant effects in aPTT. Both produced mild, comparable anticoagulant activity in TT. Anti-Xa and anti-IIa values were similar across sources. Molecular weight profiles were also comparable (ovine: 16.8 ± 0.24 kDa vs porcine: 18.02 ± 0.32 kDa). DNA content showed no significant difference (ovine: 75.78 μg vs porcine: 79 μg/10 μg API).ConclusionOvine- and porcine-derived defibrotide demonstrated equivalent coagulation, molecular, and DNA content profiles. These findings suggest ovine mucosa is a viable alternative source for defibrotide, potentially improving accessibility, reducing cost, and addressing dietary restrictions associated with porcine-derived products.
Abourahma et al. (Thu,) studied this question.