In spite of the wide use of oral anticoagulant therapy, skin necrosis remains an infrequent complication. A thorough search of the earlier scientific literature in English revealed sporadic cases that cannot supply enough data about the nature of this rare phenomenon. More current articles have examined this complication with recently developed and more sophisticated hematologic tests. A summary and analysis of all reported cases (a total of 105) were undertaken, in an attempt to find a common denominator that would identify the possible cause(s) of the condition, thereby allowing for improved treatment. An imbalance between clotting factors, due to lack of protein C or factor VII, seems to be the most reasonable explanation for the phenomenon, although data to validate this theory are lacking.Skin necrosis following oral anticoagulant therapy remains a rare complication in spite of its worldwide usage. During the last 30 years, the literature concerning this phenomenon has been based on case reports alone. In an attempt to find a common denominator for all these cases, a thorough literature search was conducted and the results were summarized.A total of 61 reports of oral anticoagulant therapy with consequent skin necrosis, with a total of 105 cases, was collected [1-61]. Of the total 105 cases, 77% were females and 23 % were males. The age of patients ranged between 16 and 90 years, with higher incidence in the fifth, sixth, and seventh decades of life (19%, 17%, and 26%, respectively) for both females and males.The causative agents, in reduced order of frequency, were Coumadin (warfarin sodium -64%) and Dicoumarol (20%). Other reported agents were Acenocoumarol (Syntron -3.8%), Phenidion (Dindevan) and Phenoprocouman (3% each), Phenylindanedion, Bishydroxycoumarin, and Dicumacyl (2% each), and combinations of Dicoumarol with Dicumacyl (1%). The necrosis appeared one to ten days after the initiation of the drug, usually after three to five days (75% of all cases).All areas of the body were affected (including face and upper extremities that had been considered immune to this phenomenon). In 27% of the cases, the lesion appeared bilaterally in the same part of the body. The affected organs were the female breast (40%), thighs (15%), and abdomen and buttocks (9%). Among males, there was a high incidence (22%) of necrosis of the genitalia (less than 2% in females). The indications for treatment with the anticoagulant were deep vein thrombosis in 40% of cases, pulmonary embolism in 11%, and both of these together in 28%. Among males, 33% of the patients had had open heart surgery.Significant medical histories included cancer in five cases, hypertension in two, obesity in 12, recent operation not related to the initiation of the drug in 10, cardiac disease in 11, diabetes in three, thalassemia minor in one, and pregnancy in two cases.Forty-seven of the 105 cases were examined histologically. The significant findings, except for the obvious necrosis, were: major bleeding (2%), minor bleeding (30%), venous thrombosis ...