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Case Report
Treatment of Catastrophic Antiphospholipid Syndrome with Defibrotide, a Proposed Vascular Endothelial Cell Modulator ARSINUR BURCOGLU-O'RAL, DORUK ERKAN, and RONALD ASHERSON
ABSTRACT.
Methods. We describe a 55-year-old man with primary APS with an intractable prothrombotic state (CAPS) resistant to combined therapy with heparin, warfarin, aspirin, and dipyridamole. Treatment with defibrotide was conducted in the context of an investigational phase II protocol where the dose was regulated and individualized by disease/patient-specific molecular and clinical markers. Results. The patient entered complete remission with defibrotide treatment. During treatment, dose dependent pharmacological actions of defibrotide and key stress markers for VEC injury were identified. Evidence of defibrotide's polypharmacology included downregulation of cytokines, notably tumor necrosis factor-a, as the earliest effect, cellular differentiation of VEC, possibly with direct regulatory effect over cellular genes, and the reversal of platelet consumption and prothrombotic state. Von Willebrand antigen levels were used as the sole marker to guide therapy. Conclusion. This case demonstrates effective remission of CAPS with defibrotide treatment. In contrast to theories that CAPS is triggered by ischemic and thrombotic tissue damage, these data present VEC injury as the primary and representative lesion of CAPS. The pathogenesis may involve concurrent impairment of different VEC functions. Achieving remission may require a polypharmacologic approach, represented here by use of defibrotide. (J Rheumatol 2002;29:2006-11) Key Indexing Terms:
CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME
From the Department of Hematology and Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Rheumatology, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, USA; Rheumatology Associates, Capetown, South Africa; and Cancer Centers of America, Southwestern Medical Center, Tulsa, Oklahoma, USA. Supported by grants from Crinos Farmacobiologica SpA, Milan, Italy, and Institute for Clinical and Scientific Research, Tulsa, OK, USA. A. Burcoglu-O'ral, MD, Cancer Centers of America, Southwestern Medical Center, Tulsa, OK; D. Erkan, MD, Department of Rheumatology, Hospital for Special Surgery, New York, NY; R. Asherson, MD, Rheumatology Associates, Capetown, South Africa. Address reprint requests to Dr. A. Burcoglu-O'ral, Cancer Centers of America/Tulsa, 2408-81st Street, Suite 100, Tulsa, OK 74137-4210. Submitted August 17, 2001; revision accepted February 7, 2002.
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