Dalteparin Helps Heal Diabetic Foot Ulcers

Prospective study shows treatment causes an increase in foot skin microcirculation and in oxygenation.

BY LESLIE SABBAGH

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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.

WHILE PROMISING, FRAGMIN TREATMENT IS NOT A REPLACEMENT FOR A FELLOWSHIP-TRAINED VASCULAR SPECIALIST.

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, a finding which "most likely indicates that dalteparin has beneficial effects on the healing process of diabetic neuroischemic foot ulcers," the authors noted.

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.

"The manuscript by Kalani and coworkers is one of the first to suggest in a reasonably robust manner that an anticoagulant may show benefit in the treatment of "neuroischemic" foot ulcers," said Dr. David G. Armstrong, when asked to comment on this article.

"While this modality suggests a potentially promising medical regime and may ultimately have a place in our respective armamentaria, it should be made clear that fragmin is not a prescriptive replacement for a fellowship-trained vascular specialist. I do look forward to further work that can confirm or refute these initially tantalizing data, he concluded. Dr. Armstrong is professor of surgery and director, Center for Lower Extremity Ambulatory Research (CLEAR) at Rosalind Franklin University of Medicine and Science, North Chicago, Ill.

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