Cutaneous necrosis revealing the coexistence of an antiphospholipid syndrome with acquired protein S deficiency, factor V Leiden and hyperhomocysteinemia

We report an exceptional case of cutaneous necrosis due to the coexistence of 4 thrombophilic factors, inherited and acquired. We would like to draw attention to these unrecognized associations. Case report: A 72-year-old woman was admitted with a 5 month history of necrotic nonhealing, painful ulcer of both legs and recently a purple toe. She had a history of 3 deep venous thromboses of the leg complicated by pulmonary embolism. A skin biopsy of the ulcer and purple toe showed only thrombosis in the dermal vessel. Laboratory findings showed a circulating lupus anticoagulant, positive anticardiolipin antibodies, antinuclear antibodies (1/320 dilution) and an anti Sm. Moreover, activated protein C resistance associated with factor V Leiden mutation and hyperhomocysteinemia was found; protein S was transiently low. With iloprost, oral anticoagulant, vitamin B 12 and folic acid, the evolution was good, with healing of ulcer. Comments: cutaneous necrosis can reveal hypercoagulable states, sometimes complex. We find 4 thrombophilic factors in our case, i.e. antiphospholipid antibodies, factor V Leiden, protein S deficiency and hyperhomocysteine mia. This is exceptional but highlights the role of several constitutional and acquired thrombophilic factors in the genesis of thrombosis. Extended protein C pathway disturbances could explain the mechanism that leads to cutaneous necrosis, in this patient, with an anti phospholipid syndrome. This case shows that it is necessary in some circumstances to make a complete hemostatic laboratory search to detect several thrombophilic factors. If they are present they can justify an oral anticoagulant treatment and a familial screening.