fibrin and Scleroderma--Localized

Venous ulceration remains a major cause of morbidity. Treatment has not improved significantly in recent years, possibly because our understanding of the pathophysiological mechanisms at work is still incomplete. We review the principal abnormalities found in the macro- and microcirculation in this condition and discuss the various theories put forward to explain the mechanism by which skin damage occurs.

Topics: Fibrin; Humans; Leukocytes; Microcirculation; Scleroderma, Localized; Skin; Skin Ulcer; Thrombosis; Venous Insufficiency; Venous Pressure

This study investigated the possibility that pericapillary fibrin deposition, found in the calf skin of patients with venous ulceration and lipodermatosclerosis, might already be present in the dermis of the gaiter area of apparently healthy limbs before any skin changes were visible. The apparently healthy limbs of 19 consecutive patients with a healed venous ulcer on one leg and no history of ulceration or clinical evidence of lipodermatosclerosis in the opposite calf, were studied. Bipedal ascending phlebography and foot volume plethysmography were performed, and systemic fibrinolytic activity and fibrinogen levels were calculated. Transcutaneous oxygen measurements were expressed as a ratio of levels from a fixed position in the gaiter skin over a control site on the arm. Biopsies of a standard site in the gaiter skin and the thigh were assessed for the presence of laminin, fibrinogen and fibronectin using immunofluorescent microscopy. The extent of pericapillary fluorescence was expressed as a ratio of the number of capillaries with deposits divided by the total number of capillaries staining with laminin (fibrin and fibronectin scores). Pericapillary fibrin deposits were observed in the dermis in 16 of the biopsies of the gaiter region (median score 0.20), and in eight of the biopsies from the thigh (median score 0.0). This difference was highly significant (P<0.01, Wilcoxon signed rank test). The transcutaneous oxygen ratio correlated negatively with the fibrin score (Spearman rank correlation coefficient -0.62, P<0.01), and there was a weak negative correlation between the half volume refilling time on foot volume plethysmography (an indicator of venous reflux) and the fibrin score (Speraman rank correlation coefficient -0.47, P<0.05). No such correlation could be shown between the fibrin score and the indicators of calf pump function, the euglobulin clot lysis time or the plasma fibrinogen. The presence of significant numbers of pericapillary fibrin deposits within the dermis of the gaiter skin has been demonstrated in 84% of this cohort of 'at risk' limbs before there is any evidence of clinical lipodermatosclerosis.

Topics: Adult; Aged; Aged, 80 and over; Blood Gas Monitoring, Transcutaneous; Capillaries; Dermis; Female; Fibrin; Fibrinolysis; Fibronectins; Humans; Leg; Male; Middle Aged; Scleroderma, Localized; Varicose Ulcer

Nonoperative therapeutic approaches to chronic venous ulceration, although effective, often require prolonged dressing care and immobilization with leg elevation. Results of skin grafting, perforator ligation, and valve interpositions and reconstructions improve results of ulcer healing but have not uniformly prevented ulcer recurrence. Our hypothesis is that reconstruction of chronic venous ulcers by excision of the diseased tissue bed and replacement with a free flap containing multiple competent microvenous valves and a normal tissue microcirculation will result in long-term cure of these debilitated patients.. Six patients with chronic venous insufficiency and recurrent ulceration (class 3) underwent excision of ulcers and surrounding liposclerotic tissue beds and reconstruction with fasciocutaneous free flaps (two bilateral). Preoperative and postoperative photoplethysmography was used to assess venous refilling times. Duplex scanning was performed to assess deep venous reflux.. There were no flap failures. Photoplethysmographic venous refilling times measured on flaps demonstrated significant immediate and long-term increases from preoperative values (all results +3 by Society of Vascular Surgery outcome grading). Long-term maintenance of tissue integrity is shown by absence of recurrent ulceration and no evidence of recurrent tissue lipodermatosclerosis in all flaps at follow-up (8 months to 7.5 years; mean 24 months). No recurrent lipodermatosclerosis was seen on flap biopsy at 2 and 7 years. Separate cadaveric injection studies, including scanning electron microscopy, revealed numerous microvenous valves directed toward the draining pedicle in the flaps used for reconstruction.. This is the first comprehensive report providing combined laboratory and clinical evaluation, anatomic rationale, and long-term outcome of surgical rehabilitation of patients with chronic venous ulceration who have undergone microsurgical flap reconstruction.

Topics: Adult; Anastomosis, Surgical; Capillaries; Chronic Disease; Female; Fibrin; Humans; Hyperplasia; Male; Microcirculation; Microsurgery; Middle Aged; Photoplethysmography; Popliteal Vein; Scleroderma, Localized; Surgical Flaps; Tibia; Ultrasonography; Varicose Ulcer; Venous Insufficiency; Venules; Wound Healing

Abnormalities in fibrin deposition are implicated in the pathogenesis of vascular occlusion in systemic sclerosis. We have used a technique that involves electrophoresis and densitometric analysis of captured fibrin- and fibrinogen-related antigens to measure the concentration of the individual fibrin and fibrinogen degradation products in 13 patients with systemic sclerosis and in 15 healthy control subjects. As a group, patients with systemic sclerosis had markedly elevated levels of total fibrin-related antigen (p = 0.0007) and D-dimer (p = 0.0004), the terminal degradation product of cross-linked fibrin. The levels of fibrin monomer, an intermediate product in the conversion of fibrinogen to cross-linked fibrin, and of D-monomer, a terminal breakdown fragment of fibrinogen and fibrin monomer, were also elevated (p less than 0.005). We conclude that patients with systemic sclerosis have evidence of enhanced fibrin formation and degradation.

Topics: Adult; Aged; Antigens; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Male; Middle Aged; Scleroderma, Localized; Scleroderma, Systemic; Sodium Dodecyl Sulfate

The clearance of radioactive fibrin from the subcutaneous tissues has been measured in the rat and in the limbs of normal subjects, patients with varicose veins, and patients with lipodermatosclerosis. The animal experiments showed that the most effective way of producing a subcutaneous deposit of fibrin was by the simultaneous injection of labelled fibrinogen and thrombin. The clearance of these clots was delayed when fibrinolysis was depressed with epsilon-aminocaproic acid. Clearance of subcutaneous fibrin in man was significantly slower in the arms of patients with varicose veins and lipodermatosclerosis. Similarly clearance in the legs of patients with lipodermatosclerosis was significantly slower than that of the normal subjects and those with uncomplicated varicose veins. The clearance of fibrin from the legs of patients with lipodermatosclerosis was significantly slower than the clearance from their arms but there was no difference between arm and leg clearance in the normal subjects and those with uncomplicated varicose veins. The patients with lipodermatosclerosis had a significantly longer dilute blood clot lysis time. The inability to clear subcutaneous fibrin may be an aetological factor of lipodermatosclerosis.

Topics: Aminocaproates; Animals; Extremities; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Rats; Rats, Inbred Strains; Scleroderma, Localized; Thrombin

Forty-one biopsy specimens, taken from the ulcer-bearing skin of 41 legs of 21 patients attending the varicose vein clinic, were selectively stained for fibrin with phosphotungstic acid haemotoxylin before being blindly assessed,. Layers of fibrin were found surrounding the dermal capillaries in all 26 legs with lipodermatosclerosis. None of the specimens from the 15 legs with clinically normal skin contained fibrin. There was also an increased number of dermal capillaries cut in cross section per high powered field in 24 of the 26 legs with lipodermatosclerosis compared with two of the 15 legs with normal skin (p less than 0.001). The mean reduction in foot vein pressure during exercise was significantly less in the 26 limbs with pericapillary fibrin than in the other 15 limbs (p less than 10(-6). Lipodermatosclerosis is synonymous with pericapillary fibrin deposition and is associated with, and probably secondary to, both a persistently raised venous pressure and an increase in the size of the dermal capillary bed. This extravascular deposition of fibrin probably stimulates tissue fibrosis and blocks the diffusion of oxygen to the overlying epidermis, producing cellular death and venous ulceration.

Topics: Capillaries; Female; Fibrin; Humans; Leg Ulcer; Male; Scleroderma, Localized; Skin; Varicose Ulcer