title: Dextran 40 reduces in vitro platelet aggregation in peripheral arterial disease.
abstract: Dextran 40 has been used to prevent post-operative thrombosis. However, its antithrombotic and antiplatelet effects in peripheral arterial disease (PAD) are poorly understood. We studied the in vitro effects of Dextran 40 on platelet function in control subjects and PAD patients using whole blood methods. Platelet function was assessed in 20 control subjects and 20 PAD patients. Spontaneous platelet aggregation (SPA) and agonist-induced platelet aggregation in response to increasing concentrations of Dextran 40 in vitro were measured by whole blood aggregometry. Flow cytometric measurements of platelet P-selectin, GpIIb/IIIa, GpIb and PAC-1 binding were also performed. There was no difference in SPA or ADP-induced aggregation in control patients with Dextran 40 in vitro. However, Dextran 40 inhibited collagen-induced aggregation in control patients (P < 0.05, Friedman test). In PAD patients, SPA and ADP (1 microM)-induced aggregation were significantly reduced by Dextran 40 in vitro (P < 0.001, Friedman test). In PAD patients, collagen-induced platelet aggregation (1 and 5 microg/ml) was significantly reduced by Dextran 40 in vitro (P < 0.01, Friedman test). GpIIb/IIIa, PAC-1 and P-selectin expression were significantly reduced in whole blood samples from PAD patients following incubation with Dextran 40 (P < 0.05, Wilcoxon rank test) but not in samples from control patients. Dextran 40 reduces spontaneous and agonist-induced platelet aggregation as well as the surface expression of markers of platelet activation in PAD patients. This antiplatelet effect may be of benefit to patients undergoing vascular surgical procedures where thrombosis is a significant risk.
authors.affiliation: Regional Vascular Unit, St Mary's Hospital, Praed St, London W2 1NY, UK.
authors.forename: P
authors.initials: P
authors.lastname: Robless
authors.forename: D
authors.initials: D
authors.lastname: Okonko
authors.forename: D P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: G
authors.initials: G
authors.lastname: Stansby
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000188:drug therapy*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests
chemical_list: D015415:Biomarkers; D003911:Dextrans; D000244:Adenosine Diphosphate; D003094:Collagen