Dalteparin-treated patients have increased foot skin microcirculation and oxygenation, resulting in better foot ulcer outcomes, compared with controls, a Swedish study has found. Dr. Majid Kalani, of the Karolinska Institutet and Danderyd Hospital, both in Stockholm, and colleagues conducted a prospective, double-blind, placebo-controlled, multicenter study to evaluate dalteparin on peripheral macro- and microcirculation and hemostatic function in 85 diabetic patients with peripheral arterial obliterative disease and chronic foot ulcers.
Inclusion criteria were toe/arm blood pressure index equal to or less than 0.6, foot ulcer duration longer than 2 months, ulcers of Wagner classification stages I and II, and aspirin 75 mg/day. Forty-three patients were randomized to subcutaneous injections of dalteparin 0.2 mL once a day, and 42 were randomized to physiological saline 0.2 mL injections once daily. Treatment continued for 6 months or until the ulcer healed, whichever came first. Ulcer outcomes were defined as healed with intact skin; improved; unchanged; impaired; or amputation above or below the ankle (Thromb. Res. 2007 Feb. 2 [Epub doi:10.1016/j.thromres.2006.12.006]).
Plasma fibrinogen, fibrin gel structure, prothrombin fragment 1+2 antigen, plasminogen activator inhibitor-1 (PAI-1) activity, and tissue plasminogen activator (TPA) antigen were analyzed at baseline and at the end of treatment. Foot skin microcirculation was measured with transcutaneous oxygen tension and laser Doppler fluxmetry (LDF).
The combined ulcer outcome results showed that the dalteparin-treated group had significantly better outcomes than did controls. Dalteparin treatment inhibited thrombin generation and increased fibrin gel porosity, thereby encouraging fibrinolysis. Dalteparin also improved fibrinolytic function by increasing TPA antigen and by blunting increases in plasma PAI-1 activity. Plasma PAI-1 activity increased significantly in the 20 controls who improved and the 13 who deteriorated, but did not significantly change in the dalteparin group.
The seven patients in the dalteparin group with impaired ulcer outcomes (two amputations; five increased ulcer area) had worse baseline peripheral macro- and microcirculation and longer time-to-peak LDF compared with baseline values in the 13 patients with improved outcomes. Two amputations were performed in the dalteparin group compared with eight in the placebo group.
The increase in local skin oxygenation in the dalteparin group “suggests improved blood distribution to nutritive capillaries due to decreased shunting of blood through arteriovenous channels,” which might explain the trend toward improved ulcer outcome in these patients, they said.