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. IntroductionPlasminogen (PLG) plays an important role in intra-and extravascular fibrinolysis, wound healing, cell migration, angiogenesis, and embryogenesis. 1 Plg is primarily synthesized by liver tissue. 2 However, other minor sources identified in mice include adrenal gland, kidney, brain, testis, heart, lung, uterus, spleen, thymus, and gut tissue. 3 In humans, the cornea has been described as an extrahepatic site of PLG synthesis. 4 Inherited PLG deficiency in humans can be divided into 2 types: true PLG deficiency (type I, or hypoplasminogenemia) and dysplasminogenemia (type II). In the former, both immunoreactive PLG level and functional activity are reduced, while the latter shows a normal or slightly reduced level of immunoreactive PLG while functional activity is significantly decreased. It has been shown by several authors since 1995 that homozygous or compound-heterozygous type I PLG deficiency is a major cause of a rare inflammatory disease affecting mainly mucous membranes in different body sites. 5,6 The most common clinical manifestation is ligneous conjunctivitis, characterized by development of fibrin-rich, woodlike ("ligneous") pseudomembranous lesions. Involvement of the cornea may result in blindness. Other, less common manifestations are ligneous gingivitis, otitis media, ligneous bronchitis and pneumonia, involvement of the gastrointestinal or female genital tract, juvenile colloid milium of the skin, and congenital occlusive hydrocephalus. 6 In severely affected patients, prognosis is poor and treatment options are few. Worldwide, more than 150 patients with this disease have been reported since 1847, the date of first description. 6,7 From the Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany; For personal use o...

In our study, coagulation screening failed to effectively identify patients at risk of bleeding.

In severe mucocutaneous bleeding episodes or joint bleeding rFVII a is of some benefit whereas in surgeries like teeth extraction, prophylactically administered rFVII a seems effective to avoid bleeding. In mild to moderate mucocutaneous bleeding events, antifibrinolytics and local measures were sufficient in most cases and the additional use of rFVII a does not seem to be necessary. Further information is needed to elaborate clear indications for the rational use of rFVII a in bleeding episodes in patients with Glanzmann thrombasthenia compared to standardized baseline treatment. This information may generate a prospective multicenter study to provide clear advice with respect to bleeding site, severity and duration.