Skin necrosis complicated by warfarin-induced protein S deficiency

Breast necrosis in a chronic user of warfarin

“…Skin necrosis is a rare condition, with incidence of 0.1 to 0.01% of cases in users of oral anticoagulant therapy whose action mechanism is the antagonism of vitamin K [1][2][3][4][5][6][7][8][9] . Flood et al described the condition for the first time in 1943 10 , but a causal relation between tissue necrosis and use of oral anticoagulants was only established in the late 1950s 11 .…”

Thrombosis Associated with Protein S Deficiency: A Case Report and Literature Review

“…It is detected in about 1:700 of the general population although its frequency is markedly increased to 3-6% in subjects with thrombophilic disorders, further indicating its pivotal role in thrombosis [4,7] . Acquired forms can occur as a result of a number of factors such as low vitamin-K levels, liver disease, HIV infection, sickle-cell anemia, and in warfarin therapy [13][14][15] . Inheritable forms are rare, with an incidence of about 0.03% [4] and usually due to large deletions in the PS gene, PROS1 [16] , although other defects such a frameshift [17] , and nonsense mutations have been described [18] .…”

“…Immunoassays can measure both free and bound forms. Careful evaluation is required to interpret the results correctly since many factors can influence serum PS levels including other diseases, pregnancy, use of oral contraceptives, insufficient vitamin-K intake, and medication with vitamin-K antagonists activity [3,13,15] . Three broad types have been described in the literature [22,23] .…”

“…In the event of presenting thrombophilic events, the initial treatment consists of unfractionated heparin or low molecular weight heparin (LWHM) in conjunction with warfarin until an INR of 2.0-3.0 is reached on two consecutive days [21,26] . Heparin should be administered for at least 5 days to prevent skin necrosis, a rare adverse effect that occurs during early warfarin treatment in patients with PS and protein C deficiency [15] . Warfarin treatment should be considered for up to 2 years, and in some cases for life-long [21] .…”

Warfarin-induced skin necrosis in a patient with protein S deficiency

“… 1 It occurs almost exclusively in patients with venous thrombosis and pulmonary embolism between the 1 st and the 10 th day after initiation of the anticoagulation. It has been associated to the deficiency of protein C and, more rarely, to the deficiency of protein S. 2 …”