Effects of Heparin Fractions on the Prevention of Skin Necrosis Resulting From Adriamycin Extravasation: An Experimental Study

In Brief Extravasation of a chemotherapeutic agent is one of the most frequent complications in cancer patients. Full-thickness skin necrosis often occurs after extravasation. Alternative approaches to treatment are local wound care, elevation, and hypothermia. It was shown that heparin prevents skin necrosis. In this experimental study, the effects of heparin fractions on the prevention of skin necrosis were compared by applying an extravasation model of Adriamycin in rats. Forty Sprague–Dawley male rats weighing 250 to 300 g were used. A total of 0.3 ml doxorubicin hydrochloride was administered subcutaneously to all rats. Ten minutes later, in the control group (group I), 1 ml normal saline was administered subcutaneously. In the first experimental group (group II), 100 U per day heparin sodium was administered in a volume of 1 ml subcutaneously. In the second experimental group (group III), nadroparin calcium (5 anti-Xa U per kilogram per day) was administered. In the third and last experimental group (group IV), dalteparin sodium (5 anti-Xa U per kilogram per day) was administered. All drugs were administered for 2 weeks. Necrotic areas were measured 4 weeks later. Statistical analysis was performed using the Kruskal–Wallis analysis of variance and the Mann–Whitney U test. Heparin fractions caused a decreased ulcer rate and size than controls (p < 0.05). There was no superiority among heparin fractions. The authors think that low-molecular weight heparins are preferred, considering the higher risk of bleeding with unfractionated heparin. In a rat model of doxorubicin-induced skin necrosis, ulcer rate and ulcer size were less when heparin or heparin fractions were administered subcutaneously. Although no difference was noted between heparin and heparin fractions, use of the fractions would be less likely to produce hemorrhage in the clinical setting.