title: Procoagulant role of microparticles in routine storage of packed red blood cells: potential risk for prothrombotic post-transfusion complications.
abstract: During routine storage, packed red blood cells (PRBC) undergo biochemical and morphological changes including loss of red blood cell (RBC) membrane asymmetry and release of microparticles (MPs) bearing phosphatidylserine (PS), a procoagulant phospholipid. This study investigated the association between PRBC storage duration, MP profile and procoagulant activity. Leukodepleted PRBC-supernatant (PRBC-SN; n=13) was prepared at weekly intervals throughout storage. Phospholipid-dependent procoagulant activity, assessed using a factor X-activated clotting time (XACT) assay, decreased throughout storage (p<0.0001), corresponding with increased procoagulant phospholipid content. As determined by flow cytometry, total numbers of MPs and of PS-bearing MPs increased by Day 28 of storage (p<0.01 and p<0.05, respectively, versus D1), and these MPs were predominantly RBC-derived (CD235+). Depletion of MPs from stored (Day 42) PRBC-SN using 0.22 μm filters reduced the number of PS-bearing MPs (p<0.01) but did not increase XACT clotting times. Furthermore, the reduction in procoagulant activity when lactadherin was used to block PS was not altered pre- or post-filtration of PRBC-SN. In conclusion, routine PRBC storage was associated with accumulation of MPs (particularly RBC-derived PS-bearing MPs) and of procoagulant phospholipids; however, depletion of PS-bearing MPs by 0.22 μm filtration did not reduce phospholipid-dependent procoagulant activity.
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Brisbane, Qld, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia.
authors.forename: Htet Htet
authors.initials: HH
authors.lastname: Aung
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Brisbane, Qld, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Tung
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Brisbane, Qld, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia.
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Dean
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Brisbane, Qld, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Flower
authors.affiliation: School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia. Electronic address: n.pecheniuk@qut.edu.au.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Pecheniuk
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods; D001793:Blood Preservation / Q000379:methods*; D055252:Cell-Derived Microparticles; D004912:Erythrocytes / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D010718:Phosphatidylserines / Q000494:pharmacology; D012306:Risk; D065227:Transfusion Reaction
chemical_list: D010718:Phosphatidylserines
keywords: Blood coagulation; blood transfusion; cell-derived microparticles; erythrocyte transfusion; phospholipids