Preclinical Evaluation of Safety and Biodistribution of Red Cell Microparticles: A Novel Hemostatic Agent

Ashish K. Rehni, Vibha Shukla, Hever Navarro Quero, Carlos Bidot, Conner R. Haase, Ensign Anise A. Crane, Shivam G. Patel, Sebastian Koch, Yeon Ahn, Wenche Jy, Kunjan R. Dave

Research output: Contribution to journalArticle

Abstract

Background: Uncontrollable bleeding is a major cause of mortality and morbidity worldwide. Effective hemostatic agents are urgently needed. Red cell microparticles (RMPs) are a highly promising hemostatic agent. This study evaluated the safety profile of RMPs preliminary to clinical trial. Methods and Results: RMPs were prepared from type O+ human red blood cell by high-pressure extrusion. Male rats were treated with RMPs either a 1 × bolus, or 4 × or 20 × administered over 60 minutes. The vehicle-treated group was used as a control. Effects on physiological parameters were evaluated; namely, blood pressure, body and head temperature, hematocrit, and blood gases. We did not observe any adverse effects of RMPs on these physiological parameters. In addition, brain, heart, and lungs of rats treated with 4 × dose (bolus followed by infusion over 60 minutes) or vehicle were examined histologically for signs of thrombosis or other indications of toxicity. No thrombosis or indications of toxicity in brain, heart, or lungs were observed. Studies revealed that RMPs were distributed mainly in liver, spleen, and lymph nodes, and were potentially excreted through the kidneys. Conclusions: Our study indicates that RMP administration appears not to have any negative impact on the parameters studied and did not produce thrombosis in heart, brain, and lungs. However, more detailed long-term studies confirming the safety of RMP as a hemostatic agent are warranted.

Original languageEnglish (US)
Pages (from-to)474-483
Number of pages10
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume24
Issue number5
DOIs
StatePublished - Sep 1 2019

Keywords

  • biodistribution
  • brain
  • heart
  • lungs
  • physiological parameters
  • thromboembolism

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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