Beneficial effects of dalteparin on haemostatic function and local tissue oxygenation in patients with diabetes, severe vascular disease, and foot ulcers

Abstract

Conclusion: Local skin oxygenation, as measured by transcutaneous oxygen tension (TcPO2) and laser Doppler fluxmetry, is improved with dalteparin in patients with diabetes, peripheral arterial disease (PAD), and chronic foot ulcers. Summary: Patients with diabetes appear to have a state of fibrinolytic dysfunction and hypercoagulation that may contribute to disturbances in skin microcirculatory function with resulting impaired healing of foot ulcers. The authors have previously reported improved outcome of patients with chronic foot ulcers and diabetes who were treated with dalteparin (Diabetes Care 2003;26:2575-80). In this study, they sought to investigate the mechanisms of the effects of dalteparin on haemostatic function and skin microcirculation. This was a prospective, randomized, double-blind, placebo-controlled trial. The study randomized 87 patients with PAD, diabetes, and chronic foot ulcers to treatment with once daily subcutaneous injections of 5000 U of dalteparin (n = 44) or placebo (n = 43). Treatment continued until ulcer healing or for a maximum of 6 months. Plasma fibrinogen, fibrin gel structure (measured by permeability coefficient and fiber mass/length ratio), prothrombin fragment 1+2 antigen, plasminogen activator inhibitor-1 activity, and tissue plasminogen activator antigen were analyzed before randomization and at the end of treatment. Skin microcirculation was assessed with laser Doppler fluxmetry and TcPO2. Measurements of permeability coefficient, fiber mass/length ratio, tissue plasminogen activator, and TcPO2 were higher (P < .05) with treatment with dalteparin compared with placebo. Baseline plasma fibrinogen and the permeability coefficient significantly correlated with TcPO2. Comment: Patients with diabetes have impaired healing. Although much of this may be due to neuropathy, microcirculatory abnormalities have long been postulated as contributing to poor healing in patients with diabetes. Some of the microcirculatory abnormalities now appear responsive to dalteparin, and there is some suggestion these effects may have clinical relevance. Work in this area is still very preliminary, but it makes sense to target the microcirculation as a site for possible intervention in patients with diabetes and foot ulcers.