Deficient fibrinolytic response in patients with Raynaud's phenomenon and its correction with defibrotide.
Twenty outpatients presenting with Raynaud's phenomenon secondary to clinical or preclinical inflammation of connective tissue were treated orally with defibrotide 400 mg three times daily or a matching placebo in a randomized double-blind study. The test product defibrotide (a polydeoxyribonucleic acid compound of animal origin with demonstrated profibrinolytic activity when administered parenterally) was administered orally for 3 weeks in order to explore its effects on the parameters of extrinsic fibrinolysis before and after venous stasis. The antigen of t-PA and its inhibitor PAI, free and total, and the biologic activity of PAI were assayed in basal conditions and after treatment. Although a marked increase of t-PA was seen with the active treatment, PAI activity was significantly reduced by defibrotide. Immunoreactive PAI was not significantly modified by treatment, even though it dropped considerably after venous stasis in the defibrotide group. Thus, the disturbance of endothelial function that seems to occur in vasculitis and in Raynaud's phenomenon secondary to inflammation of connective tissue (or so suspected to be) would constitute the basis of a disturbance of fibrinolysis, which oral defibrotide seems able to correct. Further studies are warranted to define the clinical effectiveness of this treatment in patients with Raynaud's phenomenon.
Cimminiello
C
C
Center of Vascular and Thrombotic Diseases, Hospital S. Carlo, Milano, Italy.
Milani
M
M
Pietra
A
A
Rossi
F
F
Aloisio
M
M
Nazzari
M
M
Bonfardeci
G
G
D000328:Adult; D001798:Blood Proteins / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011089:Polydeoxyribonucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D011928:Raynaud Disease / Q000097:blood* / Q000188:drug therapy
D001798:Blood Proteins; D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide