Disruption of PF4/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH)
Thrombosis and Haemostasis, 04/09/2012
Joglekar MV et al. – The studies suggest that 2–O, 3–O desulfated heparin (ODSH) can be used concurrently with unfractionated heparin (UFH) to disrupt platelet factor 4 (PF4)/H charge interactions and provides a novel strategy to reduce antibody mediated complications in heparin–induced thrombocytopenia (HIT).Methods
- The authors tested a minimally anticoagulant compound (2–O, 3–O desulfated heparin, ODSH) with preserved charge to disrupt PF4/H complex formation and immunogenicity.
- The authors show that ODSH disrupts complexes when added to pre–formed PF4/H ULCs and prevents ULC formation when incubated simultaneously with PF4 and UFH.
- In other studies, the authors show that excess ODSH reduces HIT antibody (Ab) binding in immunoassays and that PF4/ODSH complexes do not cross–react with HIT Abs.
- When ODSH and unfractionated heparin (UFH) are mixed at equimolar concentrations, the authors show that there is a negligible effect on amount of protamine required for heparin neutralisation and reduced immunogenicity of PF4/UFH in the presence of ODSH.