PMID- 31035782 OWN - NLM STAT- MEDLINE DCOM- 20200615 LR - 20201219 IS - 1940-4034 (Electronic) IS - 1074-2484 (Print) IS - 1074-2484 (Linking) VI - 24 IP - 5 DP - 2019 Sep TI - Preclinical Evaluation of Safety and Biodistribution of Red Cell Microparticles: A Novel Hemostatic Agent. PG - 474-483 LID - 10.1177/1074248419838512 [doi] AB - 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 x bolus, or 4 x or 20 x 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 x 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. FAU - Rehni, Ashish K AU - Rehni AK AD - 1 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA. AD - 2 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Shukla, Vibha AU - Shukla V AD - 1 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA. AD - 2 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Navarro Quero, Hever AU - Navarro Quero H AD - 3 Wallace H Coulter Platelet Laboratory, Division of Hematology and Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Bidot, Carlos Jr AU - Bidot C Jr AD - 3 Wallace H Coulter Platelet Laboratory, Division of Hematology and Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Haase, Conner R AU - Haase CR AD - 1 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA. AD - 2 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Crane, Ensign Anise A AU - Crane EAA AD - 1 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA. AD - 2 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Patel, Shivam G AU - Patel SG AUID- ORCID: 0000-0002-6776-5206 AD - 1 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA. AD - 2 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Koch, Sebastian AU - Koch S AD - 1 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Ahn, Yeon S AU - Ahn YS AD - 3 Wallace H Coulter Platelet Laboratory, Division of Hematology and Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Jy, Wenche AU - Jy W AD - 3 Wallace H Coulter Platelet Laboratory, Division of Hematology and Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Dave, Kunjan R AU - Dave KR AUID- ORCID: 0000-0002-0173-5338 AD - 1 Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA. AD - 2 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA. AD - 4 Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, USA. LA - eng GR - R21 NS094896/NS/NINDS NIH HHS/United States GR - R33 NS094896/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190429 PL - United States TA - J Cardiovasc Pharmacol Ther JT - Journal of cardiovascular pharmacology and therapeutics JID - 9602617 SB - IM MH - Animals MH - Cell-Derived Microparticles/*metabolism/*transplantation MH - *Erythrocyte Transfusion/adverse effects MH - Erythrocytes/*metabolism MH - *Hemostasis MH - *Hemostatic Techniques/adverse effects MH - Humans MH - Male MH - Rats, Sprague-Dawley MH - Time Factors MH - Tissue Distribution PMC - PMC7745738 MID - NIHMS1649793 OTO - NOTNLM OT - biodistribution OT - brain OT - heart OT - lungs OT - physiological parameters OT - thromboembolism COIS- Declaration of conflicting interests: The author(s) declare the following potential conflics of interest with respect to the research, authorship, and/or publication of this article: RxMP Therapeutics provided the testing material for the study. Dr. Ahn, Dr. Jy, and the University of Miami have partial ownership in RxMP Therapeutics. Drs. Ahn and Jy also received a grant support from RxMP Therapeutics. Drs. Ahn and Jy are the inventers of 2 US patents related to red cell microparticles. EDAT- 2019/05/01 06:00 MHDA- 2020/06/17 06:00 PMCR- 2020/12/17 CRDT- 2019/05/01 06:00 PHST- 2019/05/01 06:00 [pubmed] PHST- 2020/06/17 06:00 [medline] PHST- 2019/05/01 06:00 [entrez] PHST- 2020/12/17 00:00 [pmc-release] AID - 10.1177/1074248419838512 [doi] PST - ppublish SO - J Cardiovasc Pharmacol Ther. 2019 Sep;24(5):474-483. doi: 10.1177/1074248419838512. Epub 2019 Apr 29.