Dextran-40 stimulates resting platelets and binds more avidly to activated platelets

Abstract

Abstract Background A programme of monitoring and treatment with low-dose 10 per cent Dextran-40 (20 ml h−1) can successfully prevent thrombotic occlusion of the carotid artery after endarterectomy. This is a clinically effective treatment, over 500 CEAs have been performed with no thrombotic strokes, but little is known about the mechanism by which low-dose Dextran-40 affects platelet-rich thrombus formation. Methods In study 1, platelets from ten patients undergoing CEA were collected in a standardized manner. The response to therapeutic doses of Dextran-40 was assessed in vitro using whole-blood flow cytometric analysis of fibrinogen binding in response to adenosine 5′-diphosphate (ADP) and thrombin. Platelet aggregation in response to ADP and collagen was recorded. In study 2, blood collected from ten normal subjects was incubated with fluorescently labelled Dextran-40 and binding was measured using flow cytometry. In these experiments blood was either first incubated for 10 min with the FITC–Dextran-40 and then activated with thrombin 0·4 units ml−1 or activated with thrombin 0·4 units ml−1 for 10 min before incubation with FITC–Dextran-40. Results In study 1, reincubation of the patients' blood with Dextran-40 increased fibrinogen binding to resting platelets by 352 per cent (P < 0·05) and to ADP-stimulated platelets by 39 per cent (P < 0·05). Dextran-40 also increased fibrinogen binding in response to thrombin although this difference was not significant (P = 0·12), and increased platelet aggregation in response to ADP (48 per cent) and collagen (32 per cent) (P < 0·05 for both). In study 2, fluorescently labelled Dextran-40 bound to the surface of resting platelets from normal subjects in a dose-dependent manner, and caused platelet activation, as measured by increased P-selectin expression. Incubation with Dextran followed by activation caused a 28 per cent increase in Dextran binding; however, if the platelets were activated first and then exposed to Dextran the binding increased 94 per cent (P = 0·001). Conclusion Low-dose Dextran-40 is very effective in preventing thromboembolic complications after CEA. However, in vitro, Dextran-40 has a direct stimulatory effect on platelets. Dextran-40 binds to platelets and shows preferential binding to activated, compared with resting, platelets. Dextran may exert a beneficial antiplatelet/antithrombotic effect in vivo by inhibiting the recruitment of activated platelets to a growing thrombus.