Background/Case Studies: Thrombocytopenia (TCP, low platelet count) is a condition resulting from a decrease in platelet production, increase in platelet destruction/consumption, or increase in splenic clearance. At low platelet counts (≤50,000/µL), surgical procedures have high bleeding risks, any minor injury may lead to excessive bleeding, and spontaneous bleeding becomes a major concern at counts ≤10,000/µL.The current standard of care (SoC) for bleeding in TCP patients is transfusion of donor platelets. However, platelet products are limited by supply shortage due to donor dependence, short shelf-life (3-5 days), and waste due to high risks of bacterial contamination, variable efficacy due to storage-related platelet activation/degranulation, immune response, and refractoriness due to alloimmunization after repeated platelet transfusions.
Study
Design/Methods: Previous research has shown SP’s in vitro platelet-mimetic hemostatic ability using healthy donor blood and the ability to mitigate bleeding in a TCP mouse hemorrhage model. Building on this, Haima Therapeutics aims to establish that 1) SP can demonstrate a hemostatic effect in TCP patient blood samples using clinically relevant ex vivo assays, and 2) SP can reduce bleeding in a large animal model of TCP.
SP was made and characterized using standard lipid nanoparticle manufacturing techniques. A variety of ex vivo assays were explored to evaluate the hemostatic function of SP spiked into TCP patient blood samples (e.g., BioFlux®, T-TAS®, and ROTEM-NATEM). Furthermore, the efficacious dose range of SP was established in an ear laceration bleeding model in busulfan-induced thrombocytopenic New Zealand White (NZW) rabbits. The endpoints for efficacy include total blood loss and rate of bleeding over time.
Results/Findings: SP spiked into TCP patient blood samples demonstrated a recovery in several clotting parameters across multiple clinically relevant ex vivo assays. Furthermore, blood loss was reduced with SP treatment compared to vehicle treatment in TCP NZW rabbits. The effect size of SP treatment was comparable (not statistically significant) to platelet transfusion (SoC). Conclusions: SP is a fully synthetic, platelet-mimicking nanotechnology with demonstrated efficacy in clinically relevant ex vivo and in vivo models of thrombocytopenia.
