Recombinant Tissue Plasminogen Activator for the Treatment of Cutaneous Infarctions in Antiphospholipid Antibody Syndrome

Abstract

Antiphospholipid antibody syndrome (APAS) commonly presents with cutaneous infarctions mimicking thromboembolic vaso-occlusive disease. Systemic anticoagulation is the standard of care for this disorder, but treatment failures can occur. The authors report the first successful treatment of cutaneous infarctions due to APAS with low-dose, intravenous tissue plasminogen activator (rTPA) in a patient who failed to improve with high-dose anticoagulation. Wound healing was associated with a marked improvement in blood flow as assessed by scanning laser Doppler. The authors recommend that patients presenting with cutaneous infarctions in the absence of atherosclerosis be evaluated for APAS, and that fibrinolytic therapy be considered if cutaneous infarction persists despite anticoagulant therapy.

Retrospective Analysis of Tissue Plasminogen Activator as an Adjuvant Treatment for Calciphylaxis

“…3,4,6 Hyperbaric oxygen therapy, depending on availability, was provided on an outpatient basis after completing the tPA protocol. Patients received ancillary treatments for wound care and débridement of necrotic tissues (eg, antiseptic wet dressings, whirlpool, 5 or operative surgical or maggot larval débridement).…”

“…4 Our approach in treating calciphylaxis is to decrease calcium deposition, restore blood flow and oxygenation to the tissues, and provide aggressive wound care with débridement of necrotic tissue. 5 In 2004, Sewell et al 6 published our group's first case report of calciphylaxis treated successfully with tPA.…”

Update on Antiphospholipid Antibody Syndrome Management

“…Digital gangrene and skin necrosis are the major thrombotic events requiring full anticoagulation with heparin (Rossini et al, 2002). Should lesions persist despite anticoagulation, some reports suggest alternative treatments (iloprost, tissue plasminogen activator, gammaglobulins, corticosteroids, plasma exchange and immunosuppressive therapy) (Frances et al, 1989;Srinivasan et al, 2001;Zahavi et al, 1993). Major cutaneous lesions may appear particularly serious in the context of multiorgan thrombotic occlusion during catastrophic APS in which combined treatments are required ( see 8.-Management of Catastrophic APS).…”

Low-Dose Tissue Plasminogen Activator for Calciphylaxis

“…Low-dose tissue plasminogen activator (tPA; alteplase) was administered according to the protocol used for other cutaneous vaso-occlusive disorders (Table). 10,11 The patient was hospitalized and given a daily 10-mg dose of alteplase intravenously for 14 days, followed by warfarin anticoagulation maintenance therapy. Also, the dialysis was intensified; the patient received hemodialysis daily for 1 week until the serum level of phosphorus normalized; then, he was maintained on hemodialysis 3 times weekly.…”

“…Thrombolytic therapy was considered a reasonable treatment choice for our patient for the following reasons: (1) there was clinical and laboratory evidence of a hypercoagulable state (history of multiple deep venous thromboses, low protein C level, and low antithrombin III level), and a hypercoagulable state has been reported in several patients with calciphylaxis [12][13][14][15][16] ; (2) fibrin thrombi were observed on histopathologic examination; (3) anticoagulation therapy has been reported effective in patients with calciphylaxis 4 ; (4) we postulated that calciphylaxis may be considered an occlusive vasculopathy (with clinical resemblance to warfarin-induced skin necrosis or type I cryoglobulinemia); and (5) we have found that low-dose tPA is effective in the treatment of other coagulopathic disorders of the cutaneous microvasculature (eg, livedoid vasculopathy 10,11 and antiphospholipid antibody syndrome). To our knowledge, therapies directed at clot lysis have not been used for calciphylaxis.…”