Skin necrosis and oral anticoagulant therapy: a review of the literature

Abstract

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 ...

Cutaneous Necrosis Over the Nose and Lower Limbs Induced by Acenocoumarol: A Case Report and Literature Review

“…Despite the widespread use of oral anticoagulant treatment, reports of skin necrosis are still unusual. Recent theories support the combined roles of local factors, a temporary unbalance of coagulation mechanisms, and genetic factor that determines a decreased level of (protein C and protein S), the two vitamin-K dependent glycoproteins that lead to a hypercoagulable state in the pathogenesis of cutaneous necrosis induced by oral anticoagulants [ 3 , 5 ]. Skin necrosis can result from endothelial damage and microthrombi development.…”

“…However, recent reports have described a late-onset presentation. Despite the lack of understanding of the pathogenesis of cutaneous necrosis, recent research has suggested that local and genetic factors, as well as a transient imbalance of coagulation mechanisms could play a role [ 3 ]. The most commonly used anticoagulant is WA, and most reports on anticoagulant-induced skin necrosis mention WA [ 4 ].…”

The breast necrosis caused by oral anticoagulant therapy

“…The etiology of breast necrosis remains unclear [1,2,5]. The sporadic nature of the condition cannot supply enough data on the this rare phenomenon [6].…”