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- Kalani, Majid, et al.
(författare)
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Beneficial effects of dalteparin on haemostatic function and local tissue oxygenation in patients with diabetes, severe vascular disease and foot ulcers.
- 2007
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Ingår i: Thrombosis research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 120:5, s. 653-61
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A state of hypercoagulation and fibrinolytic dysfunction is present in individuals with diabetes, which may contribute to disturbed skin microcirculation and impaired ulcer healing. We have previously reported an improved outcome of chronic diabetic foot ulcers during treatment with dalteparin. In the present study we investigated the effects of dalteparin on skin microcirculation and haemostatic function. MATERIALS AND METHODS: 87 patients with diabetes, peripheral arterial obliterative disease and chronic foot ulcers were investigated in a prospective, randomised, double-blind and placebo-controlled study. They were randomised to treatment with subcutaneous injections of 5000 U dalteparin (n=44) or placebo (n=43), once daily until ulcer healing or for a maximum of six months. Plasma fibrinogen, fibrin gel structure [permeability coefficient (Ks) and fiber mass/length ratio (mu)], prothrombin fragment 1+2 (F1+2) antigen, plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator (tPA) antigen were analysed before randomization (baseline value), and at the end of the treatment period. The skin microcirculation of the foot was investigated by transcutaneous oxygen tension (TcPO(2)) and laser Doppler fluxmetry (LDF). RESULTS: The changes (Delta-values) of Ks, mu, tPA and TcPO(2) were higher (p<0.05) during treatment with dalteparin, as compared to the changes during treatment with placebo. At baseline, plasma fibrinogen and Ks were significantly correlated to TcPO(2). CONCLUSIONS: Local skin oxygenation improved and a less thrombogenic fibrin gel structure was formed in patients treated with dalteparin. Beneficial effects on haemostatic function are likely to contribute to the improved skin oxygenation observed during treatment with dalteparin.
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| 2. |
- Kalani, Majid
(författare)
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Diabetic skin microangiopathy : studies on pathogenesis and treatment
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Most of late diabetic complications have their basis in a disturbed microcirculation, i.e. diabetic microangiopathy. This along with peripheral arterial occlusive disease (PAOD) and neuropathy contribute to the development of chronic diabetic foot ulcers, a severe and expensive complication often leading to lower-limb amputations and an increased death rate. Hypercoagulation and impaired fibrinolysis associated with diabetes mellitus might contribute to the pathogenesis of diabetic microangiopathy. Aims: 1. To study the effects of the low molecular weight heparin compound dalteparin (Fragmin®, Pharmacia Corporation/Pfizer) on a) ulcer outcome, b) peripheral macro- and microcirculation, and c) haemostatic function, in patients with diabetes, PAOD and chronic foot ulcers; 2. To evaluate the predictive values of macro- (toe blood pressure, TBP) and microcirculatory (transcutaneous oxygen tension, TcP02) measurements for ulcer outcome in patients with diabetes. Methods: 1. Prospective, randomised, double-blind and placebo-controlled multicenter study. The patients were randomised to treatment with daily injections of 5000 U dalteparin or placebo, until ulcer healing or for a maximum of six months. Ulcer healing was evaluated every fourth week, and peripheral circulation and haemostatic function at baseline, after 3 and 6 months, or earlier in case of discontinuation of treatment. Foot skin microcirculation was evaluated by TcP02 and laser Doppler fluxmetry (LDF), and haemostatic function by analysis of plasma fibrinogen concentration, fibrin gel structure (permeability coefficient, Ks; fiber mass/length ratio, µ), prothrombin fragment 1+2 (F 1+2), plasminogen activator inhibitor-1 (PAI-1) activity, von Willebrand factor (vWF) and tissue plasminogen activator (tPA) antigen; 2. Prospective study enrolling 50 patients with diabetes and chronic foot ulcers. TBP and TcP02 were measured at baseline, and the ulcer outcome was evaluated every 4-6 weeks during 12 months. Results: 85 out of 87 patients completed the study protocol, of which 43 were randomised to dalteparin and 42 to placebo. Ulcer outcome was significantly (p=0.042) better in the dalteparin group, as compared to the placebo group. More patients healed with intact skin or decreased the ulcer area >=50%, and the amputation rate was reduced to 25% in the dalteparin group. Skin microcirculation: TcPO2 improved significantly (p=0.01 5) during treatment with dalteparin. Skin vasodilatory response to local heating measured by LDF improved significantly in dalteparin treated patients who showed an improved ulcer outcome. Haemostatic function: Ks and µ increased significantly during treatment with dalteparin, while plasma fibrinogen concentration was unchanged. High plasma fibrinogen and a tight fibrin gel structure were associated with impaired skin microcirculation. Plasma tPA antigen and vWF increased during treatment with dalteparin, while F 1 +2 and PAI-1 activity increased significantly in patients on placebo. Prediction of ulcer outcome: Measurement of TcP02 provided a higher positive predictive value (79%; cut-off 25 mmHg) than TBP (67%; cut-off 30 mmHg). Conclusions: Treatment with a daily dose of 5000 U dalteparin, as an adjunct to a multidisciplinary treatment programme, improves ulcer outcome and skin microcirculation in patients with diabetes and neuro-ischaemic foot ulcers. Impaired local skin microcirculation in these patients is associated with hyperfibrinogenaemia and a tight and rigid fibrin gel structure. Treatment with dalteparin exerts an inhibitory effect on thrombin generation, improves fibrinolytic function and increases fibrin gel porosity, which most probably conduce to the beneficial effects of dalteparin on the local foot skin microcirculation and the outcome of neuro-ischaemic foot ulcers in patients with diabetes.
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| 3. |
- Kalani, Majid, et al.
(författare)
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Effect of dalteparin on healing of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease: a prospective, randomized, double-blind, placebo-controlled study.
- 2003
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:9, s. 2575-80
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Tidskriftsartikel (refereegranskat)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 5000 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 chi(2) 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 >or=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 >or=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.
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| 4. |
- Torffvit, Ole, et al.
(författare)
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Increased Urine IgM and IgG2 Levels, Indicating Decreased Glomerular Size Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2 Diabetes
- 2012
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Ingår i: Biochemistry Research International. - : Hindawi Limited. - 2090-2247 .- 2090-2255. ; 2012, s. 480529-
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Tidskriftsartikel (refereegranskat)abstract
- Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were randomised to treatment with 5000 IU of dalteparin, (n = 28), or physiological saline, (n = 26), once daily until ulcer healing or for a maximum of 6 months. Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary levels of IgM and IgG2 were elevated in 47 and 50 patients, respectively. Elevated urinary levels of IgM and IgG2 indicate decreased glomerular size selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1 levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P < 0.001) and serum IGFBP-1 (P < 0.05) while no significant effects were seen in any of the other studied parameters. In conclusion, dalteparin therapy in patients with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG2 despite significantly increased glycosaminoglycans in urine. Elevated urinary levels of IgM and IgG2 might be more sensitive markers of renal disease than albuminuria in patients with type 2 diabetes and antihypertensive therapy.
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