Livedoid Vasculopathy Associated With Plasminogen Activator Inhibitor-1 Promoter Homozygosity (4G/4G) Treated Successfully With Tissue Plasminogen Activator

Abstract

Background: Livedoid vasculopathy (LV) is an occlusive thrombotic disease that affects primarily the small blood vessels of the lower extremities and often is associated with recurrent painful ulcerations. The pathogenesis of LV is unclear, but the disease is largely attributed to a hypercoagulable state. Factor V Leiden mutation, heterozygous protein C deficiency, homozygous hyperhomocysteinemia, and other inherited thrombophilias have been associated with LV. Plasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of the fibrinolytic system. Elevated levels of PAI-1 are found in some patients with thrombotic diseases. Some of these patients are homozygous for an allele of PAI-1 containing a stretch of 4 guanines at base −675 in the promoter region. This variant is associated with elevated PAI-1 protein levels, impaired fibrinolysis, and increased risk of thrombosis.Observations: A 33-year-old white woman had a 3-month history of painful enlarging ulcers on both ankles. Various therapies, including administration of oral antibiotic agents and prednisone up to 100 mg/d, to treat presumed vasculitis, were unsuccessful. Skin biopsy specimens revealed numerous thick-walled small blood ves-

Vasculopatia livedoide: uma doença cutânea intrigante

“…8,18 Other associations related to the etiopathogenesis of LV are the presence of high levels of plasminogen activator inhibitor-1 (PAI-1) and increased levels of lipoprotein(a). 19,20 Table 1 summarizes possible etiopathogenic associations in LV.…”

“…21,22 One of the possible causes of LV is the presence of reduced fibrinolytic activity in the blood of these patients, with reduced release of tissue plasminogen activator from vessel walls ( Figure 4). 19,[23][24][25] These patients' platelets also demonstrate increased aggregation activity. 21 The levels of fibrinopeptide A, which are involved in the formation of fibrin polymers in activity, characterizing a thrombogenic state, may also be elevated ( Figure 5).…”

“…38,[72][73][74] Tissue plasminogen activator inhibitor (PAI-1) is an important inhibitor of the fibrinolytic system. 19 It consists of a single-chain glycoprotein synthesized in the liver, adipose tissue and endothelial cells. 19 PAI-1 is the primary inhibitor of both t-PA and urokinasetype plasminogen activator.…”

“…19 It consists of a single-chain glycoprotein synthesized in the liver, adipose tissue and endothelial cells. 19 PAI-1 is the primary inhibitor of both t-PA and urokinasetype plasminogen activator. 19 Synthesis of PAI-1 is induced under the regulation of mediators such as endotoxin, IL-1, TNF-α, TGF-2 and lipids.…”

“…19 PAI-1 is the primary inhibitor of both t-PA and urokinasetype plasminogen activator. 19 Synthesis of PAI-1 is induced under the regulation of mediators such as endotoxin, IL-1, TNF-α, TGF-2 and lipids. 72 The discovery of genetic polymorphisms of the PAI-1 promoter clarified more information about its function.…”