fibrin and Skin-Ulcer

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

To assess thrombin generation, fibrin formation, and structure together with the fibrinolytic status in patients with systemic sclerosis (SSc) in relation to the occurrence of digital ulcers (DUs) during the course of disease.. We studied variables of endothelial dysfunction, thrombin generation, overall hemostatic potential, and fibrin clot turbidity in plasma from 58 patients with SSc (39 with DU history and 19 DU-naïve) and 46 matched healthy controls (HCs). Fibrin structure was visualized using scanning electron microscopy (SEM). Finally, 39 patients with a history of DUs were followed for 1.5 years and the predictive value of all investigated markers for new DU onset was explored.. Significantly enhanced endogenous thrombin potential (ETP) and prolonged clot lysis time (CLT) were found in patients with DUs compared to HCs. CLT was prolonged in patients with DUs compared to those without, showing good validity in identifying DUs with an area under the curve of 0.7 (95% CI 0.6-0.8). The levels of ETP and intercellular adhesion molecule 1 were independently associated with CLT. Over the follow-up period, 20 patients developed new DUs. CLT was prolonged (. Our results suggest that impaired fibrinolysis might have an emerging role in underlying digital vasculopathy and its progression in SSc.

Topics: Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Humans; Scleroderma, Systemic; Skin Ulcer; Thrombin; Thrombosis; Ulcer

Topics: Female; Fibrin; Humans; Middle Aged; Platelet-Rich Plasma; Scleroderma, Systemic; Skin Ulcer; Toes; Treatment Outcome; Wound Healing

In systemic sclerosis (SSc), chronic and uncontrolled overexpression of vascular endothelial growth factor (VEGF) results in chaotic vessels, and intractable fingertip ulcers. Vice versa, VEGF is a potent mediator of angiogenesis if temporally and spatially controlled. We have addressed this therapeutic dilemma in SSc by a novel approach using a VEGF121 variant that covalently binds to fibrin and gets released on demand by cellular enzymatic activity. Using University of California at Davis (UCD)-206 chickens, we tested the hypothesis that cell-demanded release of fibrin-bound VEGF121 leads to the formation of stable blood vessels, and clinical improvement of ischaemic lesions.. Ninety-one early and late ischaemic comb and neck skin lesions of UCD-206 chickens were treated locally with VEGF121-fibrin, fibrin alone, or left untreated. After 1 week of treatment the clinical outcome was assessed. Angiogenesis was studied by immunofluorescence staining of vascular markers quantitatively analysed using TissueQuest.. Overall, 79.3% of the lesions treated with VEGF121-fibrin showed clinical improvement, whereas 71.0% of fibrin treated controls, and 93.1% of untreated lesions deteriorated. This was accompanied by significantly increased growth of stable microvessels, upregulation of the proangiogenic VEGFR-2 and its regulator TAL-1, and increase of endogenous endothelial VEGF expression.. Our findings in the avian model of SSc suggest that cell-demanded release of VEGF121 from fibrin matrix induces controlled angiogenesis by differential regulation of VEGFR-1 and VEGFR-2 expression, shifting the balance towards the proangiogenic VEGFR-2. The study shows the potential of covalently conjugated VEGF-fibrin matrices for the therapy of ischaemic lesions such as fingertip ulcers.

Topics: Animals; Chickens; Disease Models, Animal; Fibrin; Neovascularization, Pathologic; Scleroderma, Systemic; Skin Ulcer; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors

Circumscribed palmar or plantar hypokeratosis was first described by Pérez et al in 2002 as a unique entity of the skin in which they reported 10 patients who presented with well-circumscribed areas of erythematous depressed or eroded skin mostly over the thenar or hypothenar eminences of the palms and less commonly on the soles. Histologically, the lesions demonstrated an abrupt drop-off in the cornified layer resulting in a broad area of hypokeratosis. Pérez et al hypothesized that these lesions were a distinctive epidermal malformation. There have been several reports since, some of which implicate trauma as an etiologic agent; however, the exact etiology remains unclear. The authors present the first case of circumscribed palmar or plantar hypokeratosis on a nonacral site (chest of a 63-year-old man) with novel histological features, including granular parakeratosis and evidence of trauma (subepidermal fibrin and ulcerations).

Topics: Biopsy; Fibrin; Foot Dermatoses; Hand Dermatoses; Humans; Male; Middle Aged; Parakeratosis; Predictive Value of Tests; Skin; Skin Ulcer; Thoracic Wall

Livedoid vasculitis is characterized clinically by smooth or depressed ivory-white scars surrounded by hyperpigmentation and telangiectasia with or without preceding purpuric infiltrated papules and plaques and histologically by intravascular deposition of fibrin. Its etiology remains obscure and therapy very difficult.. Our purpose was to test the efficacy of low-dose danazol in the treatment of livedoid vasculitis.. Seven patients with active lesions of livedoid vasculitis were treated with low-dose danazol (200 mg, orally, daily). Laboratory coagulation and fibrinolysis parameters, including antithrombin III, protein C, protein S, tissue plasminogen activator, plasminogen, alpha 2-antiplasmin and fibrinogen, were evaluated before and during the therapy.. Six of the 7 patients completed the treatment. After the therapy, all 6 patients had rapid cessation of new lesion formation, prompt reduction in their pain and healing of ulcers. A significant elevation of plasminogen and a decrease in fibrinogen levels were noted 1 month after initiation of the therapy (p = 0.028). The level of fibrinogen seemed to parallel the disease activity in individual patients. In addition, in most of these patients, the levels of antithrombin III, protein C, protein S and alpha 2-antiplasmin tended to increase after the treatment. However, the differences were not statistically significant. Abnormalities of tissue plasminogen activator levels were less consistent. Low-dose danazol was well tolerated without major side effects.. We concluded that low-dose danazol was effective in the treatment of livedoid vasculitis, without unacceptable side effects.

Topics: Administration, Oral; Adult; alpha-2-Antiplasmin; Antithrombin III; Blood Coagulation; Blood Vessels; Cicatrix; Danazol; Estrogen Antagonists; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hyperpigmentation; Male; Plasminogen; Protein C; Protein S; Purpura; Remission Induction; Safety; Skin Diseases, Vascular; Skin Ulcer; Telangiectasis; Tissue Plasminogen Activator; Vasculitis; Wound Healing

Topics: Bandages, Hydrocolloid; Colloids; Fibrin; Humans; Occlusive Dressings; Skin Ulcer; Wound Healing

Atrophie blanche is an uncommon condition characterized by the development of white atrophic patches of skin on the lower extremities, which form as a result of fibrinoid vasculitis of superficial and mid-dermal vessels followed by necrosis and ulceration of the epidermis. We report four cases in which similar lesions developed on the legs and ankles of young Jewish Russian immigrants to Israel. Although the lesions share many features with atrophie blanche, they differ in their early age of onset, the male predilection, and the extension of the fibrinoid vasculitic process into the subcutaneous tissue. Additionally, the peculiar population clustering (Georgia, U.S.S.R.), common ethnic background, and a family history of similar lesions in close relatives seem to point to a familial or genetic predisposition underlying the development of the disease.

Topics: Adolescent; Adult; Atrophy; Biopsy; Capillaries; Female; Fibrin; Humans; Leg Ulcer; Male; Necrosis; Skin; Skin Ulcer; Vasculitis

Topics: Angiomatosis; Anticoagulants; Arm; Biopsy; Blindness; Blood Coagulation Disorders; Capillaries; Chronic Disease; Factor V; Factor VIII; Female; Fibrin; Fibrinolysin; Humans; Leg Dermatoses; Middle Aged; Pain; Prednisolone; Skin Manifestations; Skin Ulcer; Thrombosis