This invention is directed to, inter alia, compositions comprised of pentosan polysulfate sodium (PPS) components and methods for making such compositions and using the same for the treatment of sickle cell disease (SCD). The disclosed compositions possess superior bioavailability as well as P-selectin blocking activity for the treatment of sickle-cell disease (SCD). Methods for using the same are additionally provided herein. Also provided herein is a method for detecting or quantifying PPS or a PPS fraction in solutions or in a biological sample obtained from an animal or an individual.