Systemic therapy with fibrinolytic agents and heparin for recalcitrant nonhealing cutaneous ulcer in the antiphospholipid syndrome

Skin ulceration is a cutaneous manifestation of the antiphospholipid syndrome (APS) and is associated with thrombosis of small dermal vessels. Numerous therapeutic agents have been used but are often ineffective. We describe the efficacy of heparin and fibrinolytic agents [urokinase and tissue plasminogen activator (tPA)] in the treatment of longstanding nonhealing cutaneous ulcers. In one patient, heparin plus low dose tPA resulted in healing. In another patient, treatment first with urokinase and heparin, and subsequently with tPA alone, resulted in healing. When the ulcer recurred secondary to severe peripheral edema, tPA plus heparin led to complete resolution of the ulcer. This suggests that fibrinolytic therapy and/or heparin may be useful in other recurrent thrombotic manifestations of the APS as well. However, it must be emphatically stressed that since life threatening adverse reactions can occur secondary to hemorrhage, this treatment should be undertaken only after extensive evaluation and close monitoring of the coagulation status.