[Pharmaceutical supply of human plasminogen replacement therapy for the treatment of ligneous conjunctivitis: Logistics for a university hospital]. / Approvisionnement hospitalier en plasminogène humain substitutif pour le traitement de la conjonctivite ligneuse : comment faire en pratique ?

In order to treat a pediatric patient with ligneous conjunctivitis secondary to congenital plasminogen deficiency, a supply of topically administered replacement human plasminogen has been required. In the absence of market approval, this blood-derived drug is managed by a temporary authorisation for nominative use, allowing monthly hospital dispensations. To ensure regulatory compliance and proper use of the drug, it took two years of interactions between various hospital departments and the laboratory to define the pharmaceutical supply chain in our hospital and allow the patient to receive treatment. The main difficulties lie in respecting the cold chain of this drug stored frozen in the bottles not ready for use. Transportation from the laboratory to the patient's home via the hospital pharmacy is carried out in calibrated conditions, ensuring a temperature below -20°C for 72h. Reception and dispensing steps were combined into a single pharmaceutical service in order to optimise transport time while ensuring the safety and traceability of the drug lots. Each month, a date is scheduled between the hospital pharmacy, the laboratory and the family to ensure that delivery and dispensing take place on the same day. Appropriate use and handling are explained to the family. However, two issues remain to be addressed by the manufacturer to facilitate future use of human plasminogen: the thermostability problem, which does not allow stays away from home longer than three days, and self-administration by the child, which is unlikely to be feasible due to handling difficulties.

Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation.

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator.

Anterior Segment Surgeries Under Topical Fresh Frozen Plasma Treatment in Ligneous Conjunctivitis.

PURPOSE: To evaluate the efficacy of topical fresh frozen plasma (FFP) therapy on clinical symptoms, findings, and prognosis after anterior segment surgeries in patients with ligneous conjunctivitis (LC). METHODS: Retrospective case note review. RESULTS: Eleven eyes of 7 cases whose remission was not achieved after medical treatment such as topical corticosteroids, cyclosporine A, and heparin were included in the study. The median age of admission was 19 (1-49) years, median duration of FFP treatment was 48 (15-79) months, median follow-up period was 62 (16-114) months, and median age at symptom onset was 12 (4-252) months. Diagnosis was made according to clinical presentations, plasminogen activities, and response to treatment. Topical FFP that was prepared in our clinic was used in all cases. Surgeries (membrane excision, eyelid surgery, deep anterior lamellar keratoplasty, and cataract surgery) were performed after at least 1 month of FFP treatment. Prosthetic contact lens was applied to one eye. During the follow-up period, recurrences requiring membrane excision and side effects from topical FFP were not observed. CONCLUSIONS: LC is a rare membranous conjunctivitis that proceeds with remissions and recurrences. When it was shown that the etiology of LC is plasminogen deficiency, FFP became the only treatment option targeting the etiology. In this study, we observed that the topical FFP is an effective treatment method that prevents recurrence and ensures regression of membranes and safer anterior segment surgeries in LC.

Treatment of ligneous conjunctivitis with fresh frozen plasm in twin babies.

Ligneous conjunctivitis is a rare form of chronic conjunctivitis. Mostly seen in childhood, it is characterized by the formation of fibrin-rich pseudomembranes in the tarsal conjunctiva. Plasminogen deficiency plays an important role in its etiology. There is no standart treatment protocol for managing this challenging condition, which can, with corneal involvement, lead to blindness. We present twin babies with ligneous conjunctivitis managed with fresh frozen plasma, topical heparin, and topical cyclosporine, without surgical excision of membranes.

Treatment of ligneous conjunctivitis with heterologous serum.

Ligneous conjunctivitis is a rare form of chronic and recurrent bilateral conjunctivitis, in which thick membranes develop on the tarsal conjunctiva and on other mucosae. We report the case of a 55-year old female patient with bilateral ligneous conjunctivitis who was successfully treated with 50% heterologous serum. There was no recurrence or side effects after one-year follow-up. We suggest the use of 50% heterologous serum should be further studied to better determine its efficacy as a treatment option for ligneous conjunctivitis.

Treatment of ligneous conjunctivitis with heterologous serum / Tratamento de conjuntivite lenhosa com soro heterólogo

ABSTRACT Ligneous conjunctivitis is a rare form of chronic and recurrent bilateral conjunctivitis, in which thick membranes develop on the tarsal conjunctiva and on other mucosae. We report the case of a 55-year old female patient with bilateral ligneous conjunctivitis who was successfully treated with 50% heterologous serum. There was no recurrence or side effects after one-year follow-up. We suggest the use of 50% heterologous serum should be further studied to better determine its efficacy as a treatment option for ligneous conjunctivitis.

RESUMO A conjuntivite lenhosa é uma forma rara de conjuntivite bilateral crônica e recorrente, na qual há formação de membranas espessas na conjuntiva tarsal e em outras mucosas. Relatamos o caso de uma paciente de 55 anos com conjuntivite lenhosa bilateral, que obteve sucesso no tratamento com soro heterólogo em concentração de 50%. Não houve recorrência após um ano de seguimento e nem efeitos colaterais ao tratamento. Dessa forma, o uso de soro heterólogo a 50% poderia ser mais estudado para melhor avaliação de sua eficácia como opção de tratamento para a conjuntivite lenhosa.

Ligneous conjunctivitis due to plasminogen deficit: Diagnostic and therapeutic approach. With literature review.

Ligneous conjunctivitis is a rare and poorly understood pathology. Infections and repeated microtraumas are often involved in acute disease flare-ups. This masquerade may lead to misdiagnosis and delayed treatment. We report two cases of ligneous conjunctivitis, describing various presentations of its natural history and focusing on the treatment of this rare disease.

Treatment of Ligneous Conjunctivitis Using Topical Plasminogen Therapy in an 8-Week-Old Female Infant.

An 8-week-old female infant presented with bilateral eyelid swelling and conjunctival membranes. She was diagnosed as having ligneous conjunctivitis. The membranes were excised but recurred despite topical cyclosporine, heparin, fresh frozen plasma, and systemic fresh frozen plasma transfusions. Topical plasminogen prevented membrane recurrence and intravenous plasminogen therapy treated systemic manifestations of the disease. [J Pediatr Ophthalmol Strabismus. 2018;55:e30-e32.].

Treatment of plasminogen deficiency patients with fresh frozen plasma.

Congenital plasminogen (Plg) deficiency leads to the development of ligneous membranes on mucosal surfaces. Here, we report our experience with local and intravenous fresh frozen plasma (FFP). We retrospectively reviewed medical files of 17 patients and their eight first-degree relatives. Conjunctivitis was the main complaint. Thirteen patients were treated both with intravenous and conjunctival FFP. Venous thrombosis did not develop in any. Genetic evaluation revealed heterogeneous mutations as well as polymorphisms. Diagnosis and treatment of Plg deficiency is challenging; topical and intravenous FFP may be an alternative treatment.

Topical Plasminogen as Adjunctive Treatment in Recurrent Ligneous Conjunctivitis.

Ligneous conjunctivitis is a rare, autosomal recessive, membranous conjunctivitis characterized by a deficiency in type 1 plasminogen. The absence of normal plasmin activity results in the formation of fibrin-rich, membranous material that typically manifests on the palpebral conjunctiva. Surgical treatment often causes irritation of the conjunctiva and accelerated recurrence of pseudomembranes. In this interventional case report, the authors document the results of treatment with topical plasminogen following conjunctival pseudomembrane excision in a 32-year-old woman. The patient underwent pseudomembrane excision in the OS followed immediately by hourly topical application of plasminogen eye drops. The plasminogen was prepared from pooled human plasma purchased under Food and Drug Administration approval from DiaPharma. Follow-up evaluation at 1 week, 1 month, and 5 months showed no evidence of recurrent pseudomembranous change. Adjunctive topical plasminogen application appears to be an effective and safe method of controlling pseudomembrane recurrence in patients with ligneous conjunctivitis.

Terapia nutricional proposta para conjuntivite lenhosa: estudo de caso e revisão de literatura / Nutritional treatment for leagnous conjuntivitis: case report and literature review and case report

RESUMO A conjuntivite lenhosa é resultante de um raro distúrbio autossômico recessivo hereditário, a deficiência de plasminogênio. Esta apresenta sintomas crônicos, como lesões conjuntivais membranosas características, inicialmente finas e com a persistência da inflamação evoluem se tornando esbranquiçadas, espessas e enrijecidas, lacrimejamento, secreção mucosa e hiperemia ocular acompanhados de espessas pseudomembranas lenhosa (PL) que recobrem a parte interior da conjuntiva tarsal. A literatura apresenta alguns tratamentos, entretanto nenhum deles alcançou a cura da doença. A terapia nutricional abordada neste estudo trata-se da combinação de nutrientes dentro dos limites estabelecidos para ingestão diária, baseada na nutrição ortomolecular, visando ao aumento da taxa de plasminogênio funcional, e a consequente redução dos sintomas associados à sua deficiência. Notou-se o desaparecimento de sintomas associados e redução do crescimento da PL, e também um aumento de 25% do plasminogênio funcional. Um aumento de 25% na dosagem de plasminogênio pode não ser altamente significativo, mas abre um respaldo para maiores estudos, pois já apresentou minimização dos sintomas da paciente.

ABSTRACT Ligneous conjunctivitis is the result of a rare inherited autosomal recessive disorder, the plasminogen deficiency. This presents chronic symptoms such as growth spongiosa meat, tearing, mucous discharge and ocular reddening accompanied by ligenous pseudomembranes (PL) coat the inside of the tarsal conjunctiva. The literature presents some treatments, but none of them reached a cure. The nutritional therapy addressed in this study is a combination of nutrients within the limits of daily intake, based on orthomolecular nutrition, aimed at increasing functional plasminogen rate, and the consequent reduction of symptoms associated with their disability. It was noted disappearance of the symptoms associated and a 25% increase in the functional plasminogen. A 25% increase in plasminogen dosage may not be highly significant, but it opens up a support for further study, as already presented reduction of symptoms of the patient.

Beyond hemostasis: the challenge of treating plasminogen deficiency. A report of three cases.

Congenital plasminogen deficiency is a rare autosomal recessive disorder, characterized by chronic mucosal membranous lesions. Although the most common clinical manifestation is eye involvement as ligneous conjunctivitis, extra-ocular lesions affecting other mucosal surfaces indicates a systemic disease. In this report we describe two cases with atypical extra-ocular involvement that includes pericarditis and recurrent hematocolpos, and one with paradoxical correlation between ocular lesions and plasminogen levels. In ligneous conjunctivitis, although different treatment strategies have been tried with mild success, the only effective therapy is topical or systemic plasminogen concentrates that are not commercially available. Unfortunately there is not either effective management for cases with multisystemic disease. Hence, treatment for plasminogen deficiency is still a challenge and the variability of the clinical spectrum in this pathology makes necessary a multidisciplinary approach.

Successful treatment of ligneous conjunctivitis with topical fresh frozen plasma in an infant.

A 6-month-old female infant presented to our clinic with bilateral eyelid swelling, yellowish-white membranes under both lids, and mucoid ocular discharge. Her aunt had similar ocular problems that were undiagnosed. The conjunctival membranes were excised and histopathological investigation of these membranes showed ligneous conjunctivitis. Further, laboratory examination revealed plasminogen deficiency. A good response was observed to topical fresh frozen plasma (FFP) treatment without systemic therapy, and the membranes did not recur during the treatment. Topical FFP treatment may facilitate rapid rehabilitation and prevent recurrence in patients with ligneous conjunctivitis.

Successful treatment of ligneous conjunctivitis with topical fresh frozen plasma in an infant / Sucesso do tratamento da conjuntivite lenhosa com uso tópico de plasma fresco congelado em uma criança

ABSTRACTA 6-month-old female infant presented to our clinic with bilateral eyelid swelling, yellowish-white membranes under both lids, and mucoid ocular discharge. Her aunt had similar ocular problems that were undiagnosed. The conjunctival membranes were excised and histopathological investigation of these membranes showed ligneous conjunctivitis. Further, laboratory examination revealed plasminogen deficiency. A good response was observed to topical fresh frozen plasma (FFP) treatment without systemic therapy, and the membranes did not recur during the treatment. Topical FFP treatment may facilitate rapid rehabilitation and prevent recurrence in patients with ligneous conjunctivitis.

RESUMOUma criança feminina com seis meses de idade se apresentou à nossa clínica com edema palpebral bilateral, membranas brancas amareladas sob as pálpebras de ambos os olhos e descarga mucosa. Sua tia já havia apresentado problemas oculares semelhantes que não foram diagnosticados. As membranas conjuntivais foram excisadas e a investigação histopatológica das membranas demonstraram conjuntivite lenhosa. O diagnóstico de deficiência de plasminogênio foi obtido a partir de um exame laboratorial. Tratamento tópico com plasma fresco congelado (FFP) sem qualquer terapia sistêmica mostrou boa resposta. Não foram observadas recorrências das membranas. O tratamento tópico com FFP pode ajudar a reabilitação rápida e prevenir a recorrência em pacientes com conjuntivite lenhosa.

A Case of Acute Pulmonary Embolism Associated with Dysplasminogenemia

The incidence of pulmonary embolism (PE) rises markedly with age, and only a few cases have been reported in younger adults. Thrombophilia has been reported as one of the predisposing factors for PE in younger adults. Here we report an extraordinary case of PE complicated with dysplasminogenemia, a rare genetic disorder resulting in hypercoagulability, in a young male. An 18-yr-old male visited an emergency room in the United States complaining chest discomfort. He was diagnosed as PE with deep vein thrombosis without apparent risk factors. Anticoagulation therapy with warfarin had been initiated and discontinued after 6 months of treatment. After returning to Korea he was tested for thrombophilia which revealed decreased activity of plasminogen and subsequent analysis of PLG gene showed heterozygous Ala620Thr mutation. He was diagnosed with PE complicated with dysplasminogenemia. Life-long anticoagulation therapy was initiated. He is currently under follow-up without clinical events for 2 yr.