DESIGN OF A PLATELET SUBSTITUTE UTILISING HOST FIBRINOGEN TO ENHANCE HAEMOSTASIS
Abstract number: P-M-245
Appleby1 J.A., Walker1 G.F., Middleton1 S.M., Goodall2 A.H.
11Research Department, Haemostatix Limited 22Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
How-to-cite Appleby JA, Walker GF, Middleton SM, Goodall AH. DESIGN OF A PLATELET SUBSTITUTE UTILISING HOST FIBRINOGEN TO ENHANCE HAEMOSTASIS. J Thromb Haemost 2007; 5 Supplement 2: P-M-245
Introduction: A novel platelet substitute is being developed as a safe replacement for platelet transfusion. The product is designed to bind host fibrinogen (Fgn) after injection and interact preferentially with activated platelets at the site of a wound.
Methods: The Fgn binding peptide Gly-Pro-Arg-Pro (GPRP) was conjugated to human albumin microparticles (MPs). FITC-labelled Fgn binding by the MPs was determined by flow cytometry. To assess MP incorporation into a fibrin clot, GPRP-MPs were added to platelet free plasma with thrombin (0.25 U/mL) and fibrin formation monitored in a Platelet Aggregation Profiler. Impedance aggregometry was used to assess MP interaction with unactivated and ADP-activated platelets in whole blood rendered thrombocytopenic by centrifugation. Bleeding was measured in busulfan-treated thrombocytopenic rabbits dosed with GRPR- (n=6) or control-MPs (n=6).
Results: GPRP-MPs bound 4 times more FITC-labelled Fgn than control MPs (p<0.001). After addition of thrombin (0.25 U/mL) and GPRP- or control-MPs to plasma, only GPRP-MPs were incorporated into the fibrin clot. Impedance aggregometry showed that GPRP-MPs in platelet-depleted blood enhanced ADP (3 muM)-induced aggregation compared with control MPs (Area Under Curve 12.42.6 vs 4.02.2 U; p<0.001; n=6). Without ADP there was little aggregation with either GPRP-MPs or control -MPs. (AUC 3.62.0 vs 1.90.2 U; p=0.19). In thrombocytopenic rabbits (platelet count 5 x106/mL 8; n=12), blood loss was reduced in rabbits receiving GPRP-MPs compared with control-MPs (9.35.5 vs 20.1 7.6 mL; p=0.02).
Conclusions: GPRP-MPs bind Fgn and exhibit haemostatic activity in vitro and in vivo. Fibrinogen-free GPRP-MPs have potential as an effective platelet substitute with significant safety and production advantages.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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