Plasminogen deficiency

Department of Clinical Medicine, Section of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Haemophilia (Impact Factor: 2.6). 12/2008; 14(6):1261-8. DOI: 10.1111/j.1365-2516.2008.01825.x
Source: PubMed


Plasminogen deficiency has emerged as a well-recognized disorder in which reduced levels of plasminogen lead to the development of pseudo membranes on mucosal surfaces, with subsequent end-organ damage of the affected tissue. Ligneous conjunctivitis is the most recognizable, well-documented, and common presentation of the clinical syndromes associated with plasminogen deficiency, although numerous other organs have been reported to be affected. Interestingly, while plasminogen deficiency was initially believed to be related to development of venous thromboembolic disease, more recent data suggest that decreased plasminogen levels may not, in and of themselves, increase the risk of thrombosis. Two types of plasminogen deficiency have been described in the literature. Type I represents a quantitative deficiency and type II a qualitative deficiency. It appears that hypoplasminogenaemia (type I deficiency) is the type most associated with pseudomembrane disease. A variety of genetic mutations has been identified recently and is reported to lead to these disorders. These defects have been identified in diverse populations, with no specific ethnic predilection. However, this disorder may have increased prevalence in areas and communities where consanguinity is more common. Despite the fact that the characteristic lesions are now better recognized and plasminogen levels are accurately and easily measured, adequate treatment of the clinical manifestations of this disorder is lacking. For ligneous conjunctivitis, a plasminogen concentrate formulated into an ophthalmologic preparation has been found to be an effective local therapy. Unfortunately, no plasminogen concentrate is currently available commercially for either systemic or local therapy.

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    • "The gastrointestinal tract, respiratory system, and genitourinary tract are often strongly affected, which may ultimately lead to organ failure and increased morbidity. However, the most noticeable clinical syndrome in these patients is ligneous conjunctivitis represented by fibrin rich lesions on the eyelids, which may be resolved by local treatment with Plg [1], [2]. Similarly, mice that harbor deficient Plg alleles (Plg−/−) develop normally into adulthood but will eventually suffer from inflammatory lesions and ulcers throughout the gastrointestinal tract, lungs, and reproductive organs [3]. "
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    ABSTRACT: The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin thickness and composition.
    Full-text · Article · Mar 2013 · PLoS ONE
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    • "Patients withboth FV and FVIII deficiency are generally diagnosed withmild or moderate mucosal bleeding [2,19]. Additionally,patients diagnosed with post circumcision bleeding ormenorrhagia have been reported [21,22]. Mucosal bleedingswere predominant in our 3 cases with FV-FVIII combineddeficiency. "
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    ABSTRACT: Objective: To retrospectively evaluate the clinical findings, laboratory data, management, and outcome in a group ofTurkish children diagnosed with rare coagulation deficiencies (RCDs) between January 1999 and June 2009. Material and Methods: The Turkish Society of Pediatric Hematology-Hemophilia-Thrombosis-Hemostasissubcommittee designed a Microsoft Excel-based questionnaire for standardized data collection and sent it to participatinginstitutions. Results: In total, 156 patients from 12 pediatric referral centers were included in the study. The cost common RCDswere as follows: FVII (n = 53 [34%]), FV (n = 24 [15.4%]), and FX (n = 23 [14.7%]) deficiency. The most common initialfinding in the patients was epistaxis, followed by ecchymosis, and gingival bleeding. Conclusion: Initial symptoms were mucosal bleeding, and fresh frozen plasma (FFP) and tranexamic acid werethe most commonly used treatments. We think that prophylactic treatment used for hemophilia patients should beconsidered as an initial therapeutic option for patients with rare factor deficiencies and a severe clinical course, and forthose with a factor deficiency that can lead to severe bleeding.
    Full-text · Article · Mar 2012 · Turkish Journal of Haematology
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    • "In normal conditions the corneal tissue is not in direct contact with blood, yet fibrinogen and components of the fibrinolytic system appear in tear fluid and their balance seems to be important in maintaining tear homeostasis. A major clinical symptom of plasminogen deficiency is ligneous conjunctivitis, in which case fibrin rich pseudomembrane is formed on the tarsal conjunctiva leading to ulceration and hyperplastic changes in the residual corneal epithelium [1] [2]. Mice, in which plasminogen genes were knocked out, developed conjunctival lesions indistinguishable from the human disease in both appearance and histology [3]. "
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    ABSTRACT: As blood coagulation factor XIII (FXIII) is of high importance in wound healing, we determined the concentrations of FXIII A and B subunits (FXIII-A and FXIII-B) and their complex (FXIII-A(2)B(2)) in normal tears and in tears from patients undergoing penetrating keratoplasty (PKP). FXIII complex and subunit concentrations were measured by highly sensitive chemiluminescent ELISAs in tears from 60 healthy volunteers and from 31 patients undergoing corneal transplantation. In non-stimulated tears from healthy volunteers, low but consistent amounts of FXIII-A and FXIII-B (medians: 2.13 μg/L and 7.22 μg/L, respectively) were measured, mostly in non-complexed form. Following stimulation of tear secretion FXIII levels moderately decreased, but if normalized to protein concentration they did not change. One day after PKP FXIII levels became highly elevated, then gradually decreased, but even on day 7 significantly exceeded pre-surgery values. The elevation of tear FXIII levels was significantly higher in PKP patients who later developed neovascularization of donor cornea. FXIII subunits are low concentration components of normal tear. The striking elevation of FXIII subunit and FXIII-A(2)B(2) concentrations after PKP suggests the involvement of FXIII in corneal wound healing. Perioperatively measured high FXIII levels in tears seem to represent a risk of neovascularization.
    Full-text · Article · Oct 2010 · Clinica chimica acta; international journal of clinical chemistry
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