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Effects of Poloxamer 188 Treatment on Sickle Cell Vaso-occlusive Crisis: Computer-Assisted Intravital Microscopy Study
  1. Anthony T. W. Cheung,
  2. Matthew S. Chan,
  3. Sahana Ramanujam,
  4. Arun Rangaswami,
  5. Kris Curl,
  6. Patricia Franklin,
  7. Ted Wun
  1. Departments of Pathology and Laboratory Medicine (A.T.W.C., M.S.C., S.R.), Pediatrics (A.R., P.F.), and Internal Medicine (Hematology/Oncology) (K.C., T.W.), UC Davis School of Medicine, Davis, CA.
  2. Supported in part by a University of California Professional Development Award (to A.T.W.C.) and discretionary gifts to the Biomedical Engineering Division, Department of Medical Pathology at the UC Davis Medical Center (to A.T.W.C.). This ancillary study is part of a phase III multicenter clinical trial on poloxamer 188; coordinated, funded, and administered by Theradex Inc., Princeton, NJ.
  3. Address correspondence to: Dr. Anthony T. W. Cheung, Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Research-III Building, Suite 3400, UC Davis Medical Center, 4645 Second Avenue, Sacramento, CA 95817; e-mail: atcheung{at}ucdavis.edu.

Abstract

Nine patients with sickle cell disease (SCD) who were hospitalized at UC Davis Medical Center for vaso-occlusive crisis (VOC) were studied as part of a randomized double-blind phase III clinical trial to investigate the real-time effects of poloxamer 188 on VOC. All patients showed significant microvascular changes from normal (steady-state) values during VOC (diminished venular diameter and red cell velocity). The patients were randomly assigned to be treated with poloxamer 188 or placebo. Poloxamer 188 (n = 4) but not placebo (n = 5) significantly reversed these microvascular changes ˜ 2 hours postinitiation of loading infusion (100 mg/kg in 1 hour). Further significant improvement induced by poloxamer 188 but not placebo was observed ≥ 7 hours postinfusion, resulting in a significant reversal of the microvascular changes to steady-state values.

Key Words
  • microcirculation
  • poloxamer 188
  • sickle cell crisis
  • vaso-occlusion

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