Ligneous cervicitis and endometritis: A gynaecological presentation of congenital plasminogen deficiency.

BACKGROUND: Congenital plasminogen deficiency is a rare autosomal recessive condition. Plasminogen deficiency is thought to result in an inability of fibrin breakdown and therefore accumulation of fibrin and formation of ligneous changes. Ligneous lesions can form on a number of mucosal membranes including the cervix and endometrium. METHODS: We report the case of a 25-year-old woman with type 1 plasminogen deficiency with ligneous cervicitis and endometritis and her treatment and clinical course over the last few years. We then review the current literature of ligneous cases of the female genital tract and discuss available treatment options. KEY RESULTS: We found 30 reported cases of ligneous lesions affecting the female genital tract, with the cervix being the most affected part. A number of treatment options have been tried by our patient and other cases in the literature. These include use of the combined oral contraceptive pill, fresh frozen plasma infusion, topical plasmin and plasminogen and trial use of plasminogen concentrate. CONCLUSIONS: This is a chronic condition requiring a multidisciplinary approach. There is currently no definitive treatment for the condition, current trials with plasminogen concentrate replacement therapy may provide a promising option for these patients in the future.

[Pseudoxanthoma elasticum-like disease with deficiency of vitamin K-dependent clotting factors and cutis laxa features]. / Pseudoxanthome élastique variant avec déficit en facteurs de coagulation vitamine K-dépendants et perte d'élasticité cutanée.

BACKGROUND: Pseudoxanthoma elasticum (PXE)-like syndrome is characterized by the association of PXE and cutis laxa (CL) features with a deficiency of vitamin K-dependent clotting factors. It was first described in 1971 and was identified as a distinct genetic entity in 2007 with analysis of the GGCX (γ-glutamyl carboxylase) gene, which is involved in congenital deficiency in vitamin K-dependent clotting factors. Here we report a new case of this extremely rare syndrome. PATIENTS AND METHODS: A 23-year-old female patient was seen for the emergence of loose and redundant skin following extensive weight loss. She also presented a deficiency of vitamin K-dependent clotting factors. Physical examination revealed excessive, leathery skin folds in the axillary and neck regions. A skin biopsy revealed polymorphous and fragmented elastic fibers in the reticular dermis. These were mineralized, as was demonstrated by Von Kossa staining. The clinical features of CL associated with the histopathological features of PXE and vitamin K-dependent clotting factor deficiency led us to a diagnosis of PXE-like syndrome. A molecular study of the GGCX gene showed compound heterozygosity. DISCUSSION: The GGCX gene is usually responsible for PXE-like syndrome. GGCX encodes a γ-glutamyl carboxylase necessary for activation of gla-proteins. Gla-proteins are involved both in coagulation factors in the liver and in the prevention of ectopic mineralization of soft tissues. Uncarboxylated forms of gla-proteins in fibroblast would thus enable mineralization and fragmentation of elastic fibers.

Investigating the Multifaceted Nature of Radiation-Induced Coagulopathies in a Göttingen Minipig Model of Hematopoietic Acute Radiation Syndrome.

Coagulopathies are well documented after acute radiation exposure at hematopoietic doses, and radiation-induced bleeding is notably one of the two main causes of mortality in the hematopoietic acute radiation syndrome. Despite this, understanding of the mechanisms by which radiation alters hemostasis and induces bleeding is still lacking. Here, male Göttingen minipigs received hematopoietic doses of 60Co gamma irradiation (total body) and coagulopathies were characterized by assessing bleeding, blood cytopenia, fibrin deposition, changes in hemostatic properties, coagulant/anticoagulant enzyme levels, and markers of inflammation, endothelial dysfunction, and barrier integrity to understand if a relationship exists between bleeding, hemostatic defects, bone marrow aplasia, inflammation, endothelial dysfunction and loss of barrier integrity. Acute radiation exposure induced coagulopathies in the Göttingen minipig model of hematopoietic acute radiation syndrome; instances of bleeding were not dependent upon thrombocytopenia. Neutropenia, alterations in hemostatic parameters and damage to the glycocalyx occurred in all animals irrespective of occurrence of bleeding. Radiation-induced bleeding was concurrent with simultaneous thrombocytopenia, anemia, neutropenia, inflammation, increased heart rate, decreased nitric oxide bioavailability and endothelial dysfunction; bleeding was not observed with the sole occurrence of a single aforementioned parameter in the absence of the others. Alteration of barrier function or clotting proteins was not observed in all cases of bleeding. Additionally, fibrin deposition was observed in the heart and lungs of decedent animals but no evidence of DIC was noted, suggesting a unique pathophysiology of radiation-induced coagulopathies. These findings suggest radiation-induced coagulopathies are the result of simultaneous damage to several key organs and biological functions, including the immune system, the inflammatory response, the bone marrow and the cardiovasculature.

Inherited plasminogen deficiency presenting as ligneous vaginitis: a case report with molecular correlation and review of the literature.

Type 1 plasminogen deficiency is an inherited and potentially life-threatening systemic disease in which patients develop pseudomembranous lesions of mucosal surfaces exposed to minor trauma. It is most commonly clinically encountered as ligneous conjunctivitis. We report the case of a 39-year-old woman with extensive involvement of the female genital tract. Microscopically, the vagina, cervix, endometrium, ovaries, and parametrial tissues showed innumerable deposits of paucicellular hyaline material with adjacent inflammation. Histochemical, immunofluorescent, and electron microscopic analyses revealed the amorphous material to be fibrin and collagen. In the plasma, functional plasminogen and plasminogen antigen levels were markedly decreased. Sequencing showed the patient to be a compound heterozygote for a missense and nonsense mutation in the plasminogen gene. Histologically, deposits in ligneous vaginitis are easily confused with amyloid or fibrinous debris. Recently, replacement therapy with plasminogen has been shown to significantly improve systemic symptoms, making ligneous mucositis a serious but treatable condition.

Fibrinogen Caracas I: a dysfibrinogenemia with a hemorrhagic diathesis associated with diminished fibrin fiber diameter and reduced fibrin gel porosity.

Fibrinogen Caracas I is a dysfibrinogenemia with a mild bleeding diathesis and a defective wound healing. We have characterized this abnormal fibrinogen using transmission electron microscopy (TEM) in combination with turbidity and permeation studies. Turbidometric and permeability analysis showed that the abnormal fibrin had a significantly decreased mass:length ratio and fiber diameter. In addition, the permeability studies of plasma fibrin clots showed that the gel porosity of the abnormal fibrinogen was reduced. Images of the abnormal fibrin structure obtained using TEM showed that the fibers were thinner, much less branched and less ordered than normal fibers. Diminished fibrin fiber diameter and reduced fibrin gel porosity have been taken as hallmarks of thrombophilic dysfibrinogenemias. The results of the present study show that these features are not necessarily predictive of thrombophilia. Further studies performed on a larger number of dysfibrinogenemias need to be conducted in order to establish the implications of these parameters on the clinical outcome.

Analysis of blood clotting factor activities in canine Legg-Calvé-Perthes' disease.

Legg-Calve-Perthes' (LCP) disease is a noninflammatory aseptic necrosis of the femoral head and neck in small-breed dogs. The etiology of the disease is not known, but ischemia resulting from vascular compression or occlusion has been proposed. A latent ischemic phase during development of the femoral epiphysis seems to be responsible for the onset of the typical clinical features of LCP disease. Ischemia might result from insufficient oxygen supply either caused by a reduced number of afferent arterial vessels or an occlusion of the efferent venous vessels by thrombosis. In humans, LCP disease has been linked to hypercoagulability and hypofibrinolysis caused by deficiencies of protein C, protein S, or resistance to activated protein C. To determine whether canine LCP disease is caused by similar deficiencies, we determined protein C, protein S, activated protein C, factor II, factor V, factor VIII:C, and AT III activities in plasma samples of 18 dogs with clinically and histopathologically verified LCP disease. All dogs had normal plasma activities of these factors, indicating that in these dogs LCP disease was not caused by deficiencies of the analyzed blood clotting factors.