title: Engineered virus-like nanoparticles reverse heparin anticoagulation more consistently than protamine in plasma from heparin-treated patients.
abstract: Heparin is widely used for anticoagulation, often requiring the subsequent administration of a reversal agent. The only approved reversal agent for heparin is protamine sulfate, which induces well described adverse reactions in patients. Previously we reported a novel class of heparin antagonists based on the bacteriophage Qβ platform, displaying polyvalent cationic motifs which bind with high affinity to heparin. Here we report heparin reversal by the most effective of these virus-like particles (VLP) in samples from patients who were administered heparin during cardiac procedures or therapeutically for treatment of various thrombotic conditions. The VLP consistently reversed heparin in these samples, including those from patients that received high doses of heparin, with greater efficiency than a negative control VLP and with significantly less variability than protamine sulfate. These results provide the first step towards validation of heparin antagonist VLPs as viable alternatives to protamine.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. agale@scripps.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gale
authors.forename: Darlene J
authors.initials: DJ
authors.lastname: Elias
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Averell
authors.forename: Paul S
authors.initials: PS
authors.lastname: Teirstein
authors.forename: Mitchell
authors.initials: M
authors.lastname: Buck
authors.forename: Steven D
authors.initials: SD
authors.lastname: Brown
authors.forename: Zinaida
authors.initials: Z
authors.lastname: Polonskaya
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Udit
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017908:Allolevivirus / Q000235:genetics / Q000378:metabolism*; D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D036022:Capsid Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006494:Heparin Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011479:Protamines / Q000494:pharmacology*; D013997:Time Factors; D014771:Virion
chemical_list: D000925:Anticoagulants; D036022:Capsid Proteins; D006494:Heparin Antagonists; D011479:Protamines; C043366:coat protein, Bacteriophage Qbeta; D006493:Heparin