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


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.
Kalani
Majid
M
Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden. majid.kalani@ds.se
Silveira
Angela
A
Blombäck
Margareta
M
Apelqvist
Jan
J
Eliasson
Björn
B
Eriksson
Jan W
JW
Fagrell
Bengt
B
Torffvit
Ole
O
Hamsten
Anders
A
Jörneskog
Gun
G
D000368:Aged; D017985:Dalteparin / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D016523:Foot Ulcer / Q000188:drug therapy*; D006487:Hemostasis; D006801:Humans; D007700:Kinetics; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D012867:Skin / Q000098:blood supply; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D017985:Dalteparin; D010100:Oxygen