Abstract Number: PB2491
Meeting: ISTH 2020 Congress
Background: Pentosan Polysulfate (PPS) has traditionally been used to treat patients with Interstitial Cystitis and more recently osteoarthritis, cancer, HIV and prion disease.
Aims: The purpose of this study is to create a comprehensive profile and comparison of several batches of PPS with unfractionated heparin. Additionally, the feasibility of protamine sulfate as a neutralizing agent to reverse the anticoagulant effects of PPS is investigated.
Methods: Various batches of PPS at 1 mg/ml were prepared in saline. For whole blood clotting profile, thromboelastography (TEG) was carried from 2.5 – 5.0 ug/ml and activated clotting time (ACT) at 25ug/mL. Clotting profile in whole blood, retrieved plasma and supplementation in normal human pooled plasma (NHP) were carried out at 100 – 0.0 ug/ml by using anticoagulant assays. Amydolytic methods were used to measure anti-Xa/ IIa effects. Thrombin generation inhibition studies (TGA) were carried out in NHP from 100 – 0.0 ug/ml. Heparin supplementation and protamine sulfate neutralization in NHP from 10 -0 ug/mL were compared to PPS batches in a logarithmic scale.
Results: All drugs produced a concentration dependent effect. Similar effects in anticoagulation assays were noted except anti-Xa assay. In TEG, significant viscoelastic changes were observed at 5ug/mL. Prolongation of ACT was observed at 25ug/mL. In TGA, concentration dependent but no significant difference in between the batches were noted. Neutralization of protamine sulfate was observed up to 12.5 ug/mL in anticoagulant assays and marginal effect on anti-protease assays. Neutralization studies indicated that protamine sulfate is a weaker neutralizing agent of PPS compared to heparin.
Conclusions: These studies suggest that multiple batches of PPS have a similar anticoagulant profile. In comparison to heparin, PPS presents itself as a 10-fold weaker anticoagulant alternative for use in a variety of clinical applications.
To cite this abstract in AMA style:Venkitasubramony V, Polisky A, Siddiqui F, Kouta A, Fareed J, Hoppensteadt D, Iqbal O, Laddu A, Jeske W. Biological and Pharmacological Profiling of Pentosan Polysulfate (PPS) in Comparison to Heparin and its Relative Neutralization by Protamine Sulfate [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/biological-and-pharmacological-profiling-of-pentosan-polysulfate-pps-in-comparison-to-heparin-and-its-relative-neutralization-by-protamine-sulfate/. Accessed May 18, 2021.
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