Effect of Dalteparin on Healing of Chronic Foot Ulcers in Diabetic Patients With Peripheral Arterial Occlusive Disease

Abstract

OBJECTIVE—Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers. RESEARCH DESIGN AND METHODS—A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5,000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1) who healed with intact skin; 2) in whom the study ulcer was improved, unchanged, or impaired; or 3) who were amputated above or below the ankle level, as compared with control subjects. RESULTS—Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided χ2 test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area ≥50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased ≥50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 ± 8 weeks in the dalteparin group compared with 16 ± 7 weeks in placebo group (NS). CONCLUSIONS—The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.

Factors related to outcome of neuroischemic/ischemic foot ulcer in diabetic patients

“…15,25 In some studies of patients with diabetes, about 10% to 15% (and sometimes as many as 30%) of patients who were considered not suitable for vascular surgery have been shown to heal without any amputation or without a major amputation, which is confirmed by the present findings. 1,13,25 As mentioned previously, studies with regard to vascular intervention, on the other hand, have focused on "limb salvage" and graft survival, 23,24,31 indicating a need to recognize and introduce decreased perfusion or impaired circulation as an indication for intervention in the diabetic foot to achieve and maintain healing and to avoid or delay a future amputation. 4,25,32,33 In conclusion, comorbidity, severity of PVD, and extent of tissue involvement were the most important factors that negatively affected the probability of healing.…”

“…12 After patients with PTA were put on low molecular heparin for a minimum of 3 months. 13 All patients were treated with acetylsalicylic acid or clopidogrel if no contraindication was present.…”

“…13,14 All patients, irrespective of intervention, were followed by the team according to protocol until a final outcome.…”

ADAMTS13 and von Willebrand factor concentrations in patients with diabetes mellitus

“…We measured ADAMTS13 in samples from patients with type 1 diabetes mellitus without macrovascular complications and in samples from a previous study on patients of mainly type 2 diabetes suffering from chronic foot ulcers [13,14].…”

Hyperbaric Oxygen in the Management of Chronic Diabetic Foot Ulcers

“…Whereas effective therapies proven by randomized controlled trials (RCTS), such as offloading, exist for neuropathic ulcers [2], there are few proven therapies for ischemic or neuroischemic ulcers. One possible exception is the use of low molecular weight heparin in neuroischemic ulcers, which has been supported by one RCT [4]: results of a larger, ongoing multicenter trial of this therapy are therefore awaited with interest.…”