ABSTRACT
Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (16%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T, P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLG proteins as a common molecular pathomechanism in type I PLG deficiency.
Subject(s)
Plasminogen/deficiency , Plasminogen/genetics , Animals , Blood Coagulation Disorders/genetics , Conjunctivitis/etiology , Conjunctivitis/genetics , Gene Expression Regulation , Genetic Carrier Screening , Humans , Mice , Mice, Knockout , Plasminogen/chemistry , Plasminogen/metabolism , Protein ConformationABSTRACT
For many years, available anticoagulant medications were limited to vitamin K antagonists, unfractionated heparin, and aspirin. However, in the past 20 years, several new agents have been developed for the treatment of thrombosis, and even more are being developed. This increasing number of medications has led to more specific treatment algorithms for the care of venous and arterial thrombotic events. As more agents become available, treatment guidelines are rapidly changing. With increasing frequency, interventional radiologists encounter patients already taking anticoagulant medications prophylactically or therapeutically, or they need to determine which anticoagulant medications need to be initiated for a particular procedure. Therefore, it has become increasingly important to understand the mechanisms, risks, and benefits of anticoagulant medications. A review of the traditional anticoagulants, their new counterparts, and their places in the medication repertoire of interventional radiology will be discussed herein.
