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IMPAIRED PERIVASCULAR FIBRIN CUFFS DISSOLUTION BY LOCO-REGIONAL FIBRINOLYSIS

P.L.Vannucchi *, R. Polignano *, M.L. Monaldi* and T. Lotti ^ * II Internal Medicine (Angiology Section) S.Maria Nuova Hospital - Florence ^ Clinical Dermatology ° - University of Florence

Background. Venous hypertension is responsible of an escaping of proteins and fibrinogen through the capillary wall directed in the interstitial space with a consequent fibrin polymerization in perivascular fibrin cuffs .
These cuffs may act as a barrier to the oxygen diffusion , leading to local ischaemia and epidermal necrosis. In order to evaluate the urokinase fibrinolytic activity against the pericapillary fibrin cuffs a loco-regional infusion of urokinase was performed in six patients with large and deep venous leg ulcers.

Methods. A loco-regional infusion was performed by Bier’s technique. In particular 100.000 urokinase unit dissolved in 100 ml of saline solution were infused in a foot vein during the complete occlusion of circulation below the knee in at least 15 min for four days.
The aim of the loco-regional infusion is to achieve the maximal tissue urokinase concentration. A 6 mm punch biopsy was taken before the first day of treatment and the last day, twenty minutes after urokinase administration, on the edge of the ulcer. Thin sections (6nm thin) were obtained with a microtome Harris CTD. Modified Todd’s autohistographic technique was performed to evaluate the cutaneous fibrinolytic activity (CFA). Direct immunofluorescence (DI) using fluoresceinate antifibrinogen antiserum was performed. Specificty of antibody includes native fibrinogen as well D,E,X,Y fibrinogen-fragments .

Results. CFA resulted increased after urokinase administration. An unchanged specific filamentous fluorescent activity (DI) was observed in perivascular space before and after the urokinase administration.

Interpretation. The increased amount of CFA show as the loco-regional urokinase administration achieve a high fibrinolytic tissue activity. The impaired fibrin cuffs dissolution after loco-regional fibrinolytic treatment suggest that the so called fibrin cuffs may be principally composed of fibrinogen fragments.