Defibrotide in the treatment of Raynaud's phenomenon in patients with progressive systemic sclerosis or essential mixed cryoglobulinemia

• Published in: Current therapeutic research Vol. 53; no. 1; pp. 48 - 58
• Main Authors: Ranieri, G., De Mitrio, V., Petruzzellis, V., Scaraggi, F.A., Quaranta, D., Dammacco, F.
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 1993; Excerpta medica
• Subjects: Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Medical sciences; Pharmacology. Drug treatments; Human; Skin disease; Mixed cryoglobulinemia; Oral administration; Animal origin; Cardiovascular disease; Anticoagulant; Deoxyribonucleotide; Fibrinolysis; Intramuscular administration; Raynaud syndrome; Chemotherapy; Treatment; Diseases of the autonomic nervous system; Scleroderma
• ISSN: 0011-393X; 1879-0313
• DOI: 10.1016/S0011-393X(05)80155-9

Defibrotide, a polydeoxyribonucleotide extracted from mammalian organs, enhances natural fibrinolysis and prostacyclin generation. The aim of this study was to evaluate the effects of this drug in patients with Raynaud's phenomenon suffering from progressive systemic sclerosis (PSS) or essential mixed cryoglobulinemia. Fourteen patients (four men and 10 women, aged 33 to 64 years) were enrolled in the study. Defibrotide was administered as follows: 1200 mg daily was infused over 2 hours for 7 days, 200 mg BID was injected intramuscularly for an additional 21 days, and 400 mg BID was administered orally for the final 12 weeks. The frequency and severity of Raynaud's attacks were monitored during the treatment using in-clinic questionnaires and patient's daily diaries. At baseline and after 1, 4, and 16 weeks of treatment, patients underwent a cold stress test, hand thermography, digital plethysmography, capillaroscopy, and cutaneous oxymetry. Blood coagulation and fibrinolysis studies were also performed. Overall clinical and instrumental assessment revealed a subjective and objective response in all patients. Statistical analysis of fibrinolytic parameters globally examined did not show any significant change at fixed times during treatment. In the PSS group, the stratified analysis demonstrated a trend toward improvement of atrest euglobulin clot lysis time, but specific assays, such as tissue plasminogen activator and plasminogen activator inhibitor-1, were not modified. The improved fibrinolysis induced by defibrotide in the PSS patients may be due to the drug's influence on the intrinsic fibrinolytic mechanism. Our study indicates that defibrotide may provide a new and interesting approach to the pharmacologic treatment of Raynaud's phenomenon associated with progressive systemic sclerosis or essential mixed cryoglobulinemia.