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1.
Article in Chinese | WPRIM | ID: wpr-880059

ABSTRACT

OBJECTIVE@#To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation.@*METHODS@#Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot.@*RESULTS@#The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2.@*CONCLUSION@#The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.


Subject(s)
Codon, Nonsense , Factor IX/metabolism , HeLa Cells , Humans , Mutation , RNA Splicing , RNA, Messenger/metabolism
2.
Med. lab ; 24(4): 273-289, 2020. ilus, graf
Article in Spanish | LILACS | ID: biblio-1283784

ABSTRACT

La hemofilia B o enfermedad de Christmas se diferenció por primera vez de la hemofilia A en 1947. Su forma clásica consiste en un trastorno hereditario de la coagulación causado por mutaciones en el gen F9, que codifica para el factor IX de la coagulación. Su herencia está ligada al cromosoma X; las mujeres son portadoras, pero se manifiesta clínicamente en hombres, aunque se han descrito casos de mujeres portadoras sintomáticas. El factor IX activado es una proteína dependiente de vitamina K, sintetizada en el hígado, que forma parte del complejo tenasa, cuya función es formar la mayor cantidad de trombina en el nuevo modelo de la coagulación basado en células. De acuerdo a la actividad del factor IX, su deficiencia se puede clasificar en leve (5% a 40%), moderada (1% a 5%), o severa (<1%). Su diagnóstico se realiza con la presencia de un TPT alargado que corrige con plasma normal y con la determinación del nivel funcional del factor IX, y se confirma con el estudio molecular que demuestra la mutación en el gen F9. Su diagnóstico diferencial incluye otras patologías como la hemofilia A. El tratamiento con factor IX recombinante es el más utilizado en la actualidad, pero se vienen desarrollando nuevas terapias con virus adeno-asociados recombinantes que prometen mejorar la calidad de vida para algunos pacientes afectados. La profilaxis juega un papel fundamental, en particular en los casos de enfermedad moderada y severa.


Hemophilia B or Christmas disease was first differentiated from hemophilia A in 1947. Its classic form consists of an inherited bleeding disorder caused by mutations in the F9 gene, which codes for coagulation factor IX. Its inheritance is linked to the X chromosome; women are carriers, but it manifests clinically in men, although cases of symptomatic women carriers have been described. Factor IX activates a vitamin K-dependent protein, synthesized in the liver, which is part of the tenase complex whose function is to form the largest amount of thrombin (factor IIa) in the new model of cell-based coagulation. According to factor IX activity, its deficiency can be classified as mild (5% to 40%), moderate (1% to 5%), and severe (<1%). The diagnosis is made when there is a prolonged TPT that corrects with normal plasma, and by assessing the functional level of factor IX. The diagnosis is confirmed by molecular analysis that demonstrates the F9 gene mutation. Its differential diagnosis includes disorders such as hemophilia A. Treatment with recombinant factor IX is widely used, but also new therapies are being developed with recombinant adeno-associated viruses that promise to improve the quality of life for some of these patients. Prophylaxis plays an important role in cases of moderate and severe disease


Subject(s)
Humans , Partial Thromboplastin Time , Factor IX , Hemophilia B , X Chromosome
3.
Rev. méd. Chile ; 147(3): 378-383, mar. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1004360

ABSTRACT

Due to blood derivative requirements, many patients with hemophilia were exposed to Hepatitis C virus infection (HCV) before the availability of HCV testing. We report a 46-year-old male with Hemophilia A with a hepatitis virus C infection since 2004 causing a cirrhosis. Due to a hepatopulmonary syndrome, he received a liver allograph using a factor VIII replacement protocol, after eradicating the virus C. He had a good postoperative evolution, and no more factor VIII was required after transplantation until his last assessment.


Subject(s)
Humans , Male , Middle Aged , Liver Transplantation/methods , Hepatitis C/complications , Hemophilia A/complications , Liver Cirrhosis/surgery , Factor IX/administration & dosage , Factor VIII/administration & dosage , Hemophilia A/therapy , Liver Cirrhosis/etiology
4.
Blood Research ; : 204-209, 2019.
Article in English | WPRIM | ID: wpr-763076

ABSTRACT

BACKGROUND: Risk factors for the development of inhibitors in previously untreated patients (PUPs) have been reported; this is not the case in previously treated patients (PTPs) owing to fewer studies. Risk factors may differ for the development of PTP versus PUP inhibitors. We aimed to identify risk factors for PTP inhibitor development. METHODS: Participants were patients at a hemophilia treatment center in Korea with current or past history of factor VIII or factor IX alloantibodies. Observed inhibitors were classified as PUP or PTP inhibitors based on the cumulative number of exposure days. We compared the type and severity of hemophilia, mutation type, and family history of inhibitor between PUPs and PTPs. Events within 3 months before the first inhibitor detection, such as change of the factor concentrate used, short-term high exposure or continuous infusion of factor concentrate, history of surgery, infection, diagnosis of cancer, use of immunosuppressive or immunomodulator agents, and vaccination were compared between PUPs and PTPs. RESULTS: We observed 5 PUP inhibitors and 5 PTP inhibitors in 115 patients with hemophilia A. Events that might be related to the development of inhibitors within 3 months prior to the first inhibitor detection were observed in all 5 PTPs. On the contrary, no such events were observed in any PUPs. The observed events included a change in the factor concentrate used, subsequent chemotherapy, and short-term high exposure to factor concentrates for controlling hemorrhage and surgeries. CONCLUSION: Our results suggest a greater role of nongenetic factors in PTP inhibitor development.


Subject(s)
Diagnosis , Drug Therapy , Factor IX , Factor VIII , Hemophilia A , Hemorrhage , Humans , Isoantibodies , Korea , Prevalence , Risk Factors , Vaccination
5.
Blood Research ; : 41-48, 2018.
Article in English | WPRIM | ID: wpr-713630

ABSTRACT

BACKGROUND: Korean National Health Insurance reimburses factor VIII (FVIII) and factor IX (FIX) clotting factor concentrate (CFC) infusions to discrepant activity levels, allowing elevation of FVIII activity to 60 IU/dL and FIX to 40 IU/dL. We aimed to assess hemostatic response to these target levels using global hemostatic assays. METHODS: We enrolled 34 normal healthy men, 34 patients with hemophilia A, and 36 with hemophilia B, with residual factor activity of 3 IU/dL or less and without inhibitors. Patients with hemophilia A and B received injected CFCs according to reimbursement guidelines. Fifteen minutes after injection, we assessed hemostatic response with global hemostatic assays: thrombin generation assay (TGA), thromboelastography (TEG), and clot waveform analysis (CWA). RESULTS: Normal healthy men and patients with hemophilia A and B were 36.7, 37.2, and 35.1 years old, respectively. FVIII and recombinant FIX concentrate doses were 28.8 IU/kg and 43.6 IU/kg. Post-infusion FVIII activity rose from 0.5 IU/dL to 69.4 IU/dL, while FIX activity rose from 1.4 IU/dL to 46.8 IU/dL. Post-infusion peak thrombin concentrations in hemophilia A and B were 116.6 nM/L and 76.4 nM/L (P < 0.001). Post-infusion endogenous thrombin potential (ETP) in hemophilia A and B was 1349.8 nM/min and 915.6 nM (P < 0.001). TEG index of hemophilia A and B was 0.11 and −0.51 (P=0.006). CONCLUSION: Current reimbursed doses for FIX concentrates are insufficient to achieve hemostatic responses comparable to those after reimbursed doses for FVIII concentrates in terms of peak thrombin concentration, ETP, and TEG index.


Subject(s)
Factor IX , Factor VIII , Hemophilia A , Hemophilia B , Humans , Male , National Health Programs , Thrombelastography , Thrombin
6.
Article in Korean | WPRIM | ID: wpr-714968

ABSTRACT

Hemophilia is an X-linked recessive disorder, which is classified into hemophilia A, defined by factor VIII deficiency and hemophilia B, defined by factor IX deficiency. The usual clinical presentation is spontaneous bleeding and prolonged activated partial thromboplastin time in a person without history of a coagulation disorder. The severity of hemophilia describes how serious a problem is and has been defined by a traditional classification into three forms: severe, moderate, mild. Hemophilia has never been reported after a rhinosinus surgery in otorhinolaryngology in Korea, but we encountered a 37-year-old man with hemophilia B who had undergone a rhinosinus surgery. He had no bleeding tendency in the past nor a family history for bleeding. But the patient presented with continuous nasal bleeding for a few days after surgery. We report this case of hemophilia B diagnosed after rhinosinus surgery that was cured with Factor IX replacement therapy with a review of the relevant literature.


Subject(s)
Adult , Classification , Endoscopy , Epistaxis , Factor IX , Hemophilia A , Hemophilia B , Hemorrhage , Humans , Korea , Otolaryngology , Partial Thromboplastin Time
7.
Brasília; CONITEC; abr. 2017.
Non-conventional in Portuguese | LILACS, BRISA | ID: biblio-906912

ABSTRACT

CONTEXTO: As coagulopatias hereditárias são doenças hemorrágicas resultantes da deficiência quantitativa e/ou qualitativa de um ou mais fatores da coagulação e se caracterizam pela ocorrência de hemorragias de gravidade variável, de forma espontânea e/ou pós-traumática. Segundo dados de 2014 do Sistema Hemovida Web ­ Coagulopatias do Ministério da Saúde, o número de pacientes com Hemofilia B era de 1.881 no Brasil. Como não há cura para as hemofilias, os objetivos de tratamento são prevenir e tratar hemorragias de modo a evitar artropatias incapacitantes e dano tecidual, e melhorar a qualidade de vida e a sobrevida. As modalidades de tratamento da hemofilia B são definidas pela periodicidade com que é realizada a reposição dos fatores de coagulação IX, podendo ser sob demanda (episódico) ou profilático. O fator IX de origem plasmática faz parte do rol de tecnologias ofertada pelo SUS para o tratamento de Hemofilia B. TECNOLOGIA: Alfanonacogue (Benefix®). INDICAÇÃO: Controle e prevenção de episódios hemorrágicos e para profilaxia de atividades rotineiras e cirúrgicas de pacientes com hemofilia B, menores de 19 anos de idade. PERGUNTA: O uso do Fator IX recombinante (BeneFIX®), além de tão eficaz quanto comparado às opções disponíveis atualmente no SUS, proporciona vantagens de segurança aos pacientes com Hemofilia B? EVIDÊNCIAS CIENTÍFICAS: Os estudos apresentados pelo demandante demonstram a eficácia do medicamento Benefix em aumentar a atividade de FIX e controlar sangramentos. Entretanto, não foi apresentado estudo de eficácia que comparasse os fatores IX plasmático e recombinante, o que impossibilita posicionar o fator IX recombinante como igual, melhor ou pior do que o fator IX plasmático ofertado pelo SUS. Apenas um estudo retrospectivo comparou o fator IX plasmático (medicamento atualmente ofertado pelo SUS) com o fator IX recombinante, e concluiu que a frequência de reações alérgicas e do desenvolvimento de inibidores entre os pacientes que receberam ambos os fatores IX foi bem similar (Recht et al., 2011). Na revisão sistemática incluída pelo DGITS sobre tipos e frequência das reações adversas - não trombóticas e não associadas a inibidor - relacionadas aos fatores de coagulação utilizados em pacientes com hemofilia A, hemofilia B e doença de von Willebrand, os autores concluíram que os dados por eles apresentados confirmam o elevado grau de segurança dos produtos atualmente utilizados para terapia de hemofilia A e B e doença da von Willebrand (Franchini et al., 2012). Assim, até o momento, não há comprovação de que os fatores IX de origem plasmática utilizados atualmente pelo SUS confiram algum risco conhecido e quantificável aos pacientes quando comparados ao Fator IX recombinante. AVALIAÇÃO ECONÔMICA: Na análise de custo-minimização, foram encontrados os seguintes custos incrementais: profilaxia primária - R$ 474.978,00; cirurgia de médio porte - R$ 27.802,00; tratamento de sangramentos espontâneos - R$ 5.014,00. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário de R$ 728 milhões a aproximadamente R$ 1,01 bilhão de reais considerando o horizonte de tempo de 5 anos possivelmente está subestimado e não se justifica frente falta de evidência de superioridade em termos de eficácia e segurança do Fator IX recombinante em relação ao Fator IX plasmático. RECOMENDAÇÃO INICIAL: Os membros presentes na reunião do plenário da Conitec realizada no dia 10 de novembro deliberaram que o tema fosse submetido à consulta pública com recomendação preliminar desfavorável a incorporação do alfanonacogue (fator IX recombinante) para o tratamento da Hemofilia B. Tal recomendação foi embasada na falta de evidências que demonstrem superioridade do medicamento Benefix frente à tecnologia já disponível no tratamento da hemofilia B, e assim, sendo, não se justificaria o impacto orçamentário apresentado. CONSULTA PÚBLICA: Foi recebido um total de 155 contribuições, sendo 146 contribuições provenientes do formulário de experiência/opinião e 9 do formulário técnico-científico. Nenhuma das contribuições apresentou evidências de superioridade do fator IX recombinante em relação ao plasmático. RECOMENDAÇÃO FINAL: Os membros presentes na reunião do plenário da Conitec realizada no dia 08 de março de 2017 mantiveram a recomendação desfavorável a incorporação do alfanonacogue (fator IX recombinante) para o tratamento da Hemofilia B. DECISÃO: Não incorporar o alfanonacogue para hemofilia B em pacientes menores de 19 anos de idade, no âmbito do Sistema Único de Saúde - SUS, dada pela Portaria nº 17, publicada no DOU nº 77, do dia 24 de abril de 2017, seção 2, pág. 57.(AU)


Subject(s)
Humans , Factor IX/administration & dosage , Hemophilia B/drug therapy , Brazil , Health Evaluation/economics , Technology Assessment, Biomedical , Unified Health System
8.
Article in English | WPRIM | ID: wpr-633717

ABSTRACT

OBJECTIVE: To identify risk factors associated with disease recurrence among Filipinos with papillary thyroid carcinoma (PTC).METHODS:Design: Retrospective Cohort StudySetting: Tertiary National University HospitalParticipants: 76 patients diagnosed with papillary thyroid carcinoma, classified as low and low-to-intermediate risk (2015 ATA classification) that underwent total thyroidectomy with or without neck dissection from 2010-2014 and were followed up from 10 months to 5 years. Log rank and Cox regression analyses were used to determine significant risk factors for recurrence.RESULTS: 29 (38.15%) had recurrence. On univariate analysis, age, tumor size, multifocality, extrathyroidal extension, presence of lateral neck nodes and RAI therapy were statistically associated with recurrence. However, on multivariate analysis, no clinicopathologic factor was statistically associated with recurrence.CONCLUSION: Age of >45 years, female sex, tumor size of >2 cm, multifocality, presence of microscopic extrathyroidal extension and lymph node metastasis might contribute to the recurrence of papillary thyroid cancer while post-operative radioactive ablation may have some protective effect. However, this study suggests that other factors must be included in the model to better understand the relationship between these factors and recurrence.


Subject(s)
Humans , Male , Female , Aged , Middle Aged , Adult , Young Adult , Adolescent , Thyroid Cancer, Papillary , Neck Dissection , Thyroidectomy , Thyroid Neoplasms , Lymphatic Metastasis , Lymph Nodes , Regression Analysis , Factor IX
10.
Chinese Journal of Biotechnology ; (12): 164-171, 2016.
Article in Chinese | WPRIM | ID: wpr-242304

ABSTRACT

Hemophilia B is an X chromosome linked hereditary hemorrhagic disease, which is caused by the lose function mutation of factor IX (FIX), and significantly affects the patients' lifespan and life quality. The severity of hemophilia B depends on the FIX level in the plasma. By referring to the relevant literatures, we reviewed and summarized hemophilia B replacement therapies. Specifically, we focus on recombinant factor IX products on the market and those in the pipeline, especially on the long-acting factor IX drugs, to provide the basis for researches of new hemophilia B drugs.


Subject(s)
Factor IX , Genetics , Therapeutic Uses , Hemophilia B , Drug Therapy , Humans , Mutation , Recombinant Proteins , Therapeutic Uses
11.
Article in English | WPRIM | ID: wpr-213687

ABSTRACT

PURPOSE: Molecular genetic analysis is the main approach used for prenatal diagnosis of hemophilia A and B. However, in certain cases, such analysis is uninformative. In such situations, direct measurement of fetal coagulation factor levels is still the best option, and it may be the only option in some cases. This study was conducted to determine the normal ranges of midtrimester cord blood factor VIII (FVIII) and IX (FIX) in a Korean population. MATERIALS AND METHODS: Twenty-six FVIII samples and 29 FIX samples were assayed in fetal cord blood acquired by ultrasound-guided cordocentesis. Sampling was conducted during gestational ages of 19-24 weeks. RESULTS: The mean and standard deviations for FVIII and FIX activity were 45.5±30.5% and 19.9±12.2%, respectively. Ranges for FVIII and FIX were 1.5-125.0% and 6.0-52.0%, respectively. CONCLUSION: Our study revealed the normal ranges and lowest level of factor VIII and factor IX in non-affected normal fetus by fetal cord blood sampling during the mid-trimester in a Korea population. The factor assay of the fetal cord blood is invasive but feasible and provides important basic data related to hemophilia.


Subject(s)
Blood Coagulation Factors , Cordocentesis , Factor IX , Factor VIII , Female , Fetal Blood , Fetus , Gestational Age , Hemophilia A , Humans , Korea , Molecular Biology , Pregnancy , Pregnancy Trimester, Second , Prenatal Diagnosis , Reference Values
12.
Neonatal Medicine ; : 238-241, 2016.
Article in English | WPRIM | ID: wpr-64412

ABSTRACT

Gastrointestinal hemorrhage in neonates is commonly associated with necrotizing enterocolitis, cow's milk protein allergy, and gastrointestinal malformation. Gastrointestinal bleeding on the first day of life, presenting as the first manifestation of a disorder, has rarely been reported associations with gastric ulceration, Salmonella infection, and allergic colitis. Hemophilia B is also a rare cause of gastrointestinal bleeding during the neonatal period. In the present case, a male infant developed repetitive hematemesis on the first day of life. His initial level of coagulation factor IX was 1.9%, and he was diagnosed with moderate hemophilia B. No further hematemesis or melena was observed during recombinant factor IX therapy. The infant did not have a family history of hemophilia. In conclusion, although gastrointestinal hemorrhage on the first day of life as the first manifestation of a disease is rare, infants who present with spontaneous gastrointestinal hemorrhage after birth and with unexplained prolonged activated partial thromboplastin time should be evaluated for coagulation factor deficiency regardless of whether they have any family history of hemophilia.


Subject(s)
Blood Coagulation Factors , Colitis , Enterocolitis, Necrotizing , Factor IX , Gastrointestinal Hemorrhage , Hematemesis , Hemophilia A , Hemophilia B , Hemorrhage , Humans , Hypersensitivity , Infant , Infant, Newborn , Male , Melena , Milk Proteins , Partial Thromboplastin Time , Parturition , Salmonella Infections , Stomach Ulcer
13.
Article in English | WPRIM | ID: wpr-788532

ABSTRACT

We are reporting our experience of oral rivaroxaban (Xarelto(R)) treatment for L-asparaginase (L-ASP)-induced deep vein thrombophlebitis in the lower extremity developed during childhood acute lymphoblastic leukemia (ALL) chemotherapy, with a brief review of the literature. A 16-year-old boy was admitted to our institution with right lower leg pain and gait difficulties. He was diagnosed with ALL and started chemotherapy protocol. He had been under a chemotherapy course of delayed intensification (DI)-1. We began antibiotics treatment for possible inflammation including cellulitis of the leg and planned an MRI scan. The MRI scan indicated thrombophlebitis of the right posterior calf deep veins. Subsequent DVT CT and coagulation profiles showed other abnormal findings. Coagulation factor assay were noted with decreased levels of multi factors; Factor II 45%, Factor IX 35.3 %, Factor X 30%, Factor XI 19%, Factor XII 22%, and anti-coagulants levels were decreased also with variant degrees; Protein C Activity 51%, Protein C Ag 54.5%, Protein S Activity 35%, Protein S Antigen, total 27.1%, Protein S Antigen, free 41.7%. Low molecular heparin (LMWH) treatment was initiated and the patient was switched to oral rivaroxaban (Xarelto(R)). After 6 weeks treatment, abnormal coagulation profiles and MRI scan showed improvement. Furthermore, the patient had no other symptoms or recurrence of thrombotic events. There was no significant adverse reaction to rivaroxaban in this patient.


Subject(s)
Adolescent , Anti-Bacterial Agents , Blood Coagulation Factors , Cellulitis , Drug Therapy , Factor IX , Factor X , Factor XI , Factor XII , Gait , Heparin , Humans , Inflammation , Leg , Lower Extremity , Magnetic Resonance Imaging , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Protein C , Protein S , Prothrombin , Recurrence , Thrombophlebitis , Veins , Rivaroxaban
14.
Rev. saúde pública ; 49: 1-13, 27/02/2015. tab, graf
Article in English | LILACS | ID: lil-742298

ABSTRACT

OBJECTIVE To review studies on the readability of package leaflets of medicinal products for human use. METHODS We conducted a systematic literature review between 2008 and 2013 using the keywords “Readability and Package Leaflet” and “Readability and Package Insert” in the academic search engine Biblioteca do Conhecimento Online, comprising different bibliographic resources/databases. The preferred reporting items for systematic reviews and meta-analyses criteria were applied to prepare the draft of the report. Quantitative and qualitative original studies were included. Opinion or review studies not written in English, Portuguese, Italian, French, or Spanish were excluded. RESULTS We identified 202 studies, of which 180 were excluded and 22 were enrolled [two enrolling healthcare professionals, 10 enrolling other type of participants (including patients), three focused on adverse reactions, and 7 descriptive studies]. The package leaflets presented various readability problems, such as complex and difficult to understand texts, small font size, or few illustrations. The main methods to assess the readability of the package leaflet were usability tests or legibility formulae. Limitations with these methods included reduced number of participants; lack of readability formulas specifically validated for specific languages (e.g., Portuguese); and absence of an assessment on patients literacy, health knowledge, cognitive skills, levels of satisfaction, and opinions. CONCLUSIONS Overall, the package leaflets presented various readability problems. In this review, some methodological limitations were identified, including the participation of a limited number of patients and healthcare professionals, the absence of prior assessments of participant literacy, humor or sense of satisfaction, or the predominance of studies not based on role-plays about the use of medicines. These limitations should be avoided in future ...


OBJECTIVO Analisar a literatura sobre legibilidade das bulas dos medicamentos para uso humano. MÉTODOS Estudo de revisão sistemática, utilizando as palavras-chave “Readability and Package Leaflet” e “Readability and Package Insert”e a ferramenta de busca académica b-on, que contém diferentes bases bibliográficas. O período analisado foi entre 2008 e 2013. Foram aplicados os critérios PRISMA para redigir o relatório da revisão. Foram incluídos artigos originais de pesquisa quantitativa ou qualitativa. Os critérios de exclusão foram: artigos de opinião ou de revisão, ou escritos numa língua diferente do inglês, português, italiano, francês ou espanhol. RESULTADOS Foram identificados 202 trabalhos, dos quais 180 foram excluídos e 22 selecionados para análise: dois com profissionais de saúde, 10 com pacientes, três sobre reações adversas e sete descritivos. As bulas apresentaram diversos problemas de legibilidade, entre os quais: textos insuficientemente claros e simples, utilização de tamanhos de letra pequenos e número reduzido de ilustrações. Os principais métodos utilizados para avaliar a legibilidade das bulas foram as fórmulas e os testes de legibilidade/usabilidade. Entre as limitações metodológicas, foram identificados aspetos como o recurso a amostras pequenas, a inexistência de fórmulas de legibilidade específicas para a língua em causa, e.g., português, e a realização de testes de compreensão em grupos de pacientes sem avaliação prévia da literacia, dos conhecimentos específicos na área da saúde, das capacidades cognitivas, ou do grau de satisfação dos participantes. CONCLUSÕES Em geral, as bulas apresentaram diversos problemas de legibilidade. Adicionalmente, nesta revisão foram identificadas algumas limitações metodológicas nos estudos revistos (e.g. a participação de um número reduzido de pacientes e profissionais de saúde, a ausência da avaliação prévia da literacia, do humor ou satisfação dos participantes ...


Subject(s)
Animals , Humans , Blood Coagulation Factors/pharmacology , Blood Coagulation Factors/therapeutic use , Hemostasis/drug effects , Antibodies, Monoclonal , Antithrombins , Antithrombin Proteins/genetics , Biotechnology , Clinical Trials as Topic , Factor IX , Factor VIIa , Factor VIII , Hemostasis/physiology , Protein Engineering , RNA Interference , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Treatment Failure , Treatment Outcome
15.
Blood Research ; : 103-108, 2015.
Article in English | WPRIM | ID: wpr-184126

ABSTRACT

BACKGROUND: Hemophilia A is caused by heterogeneous mutations in F8. Coagulation factor VIII (FVIII), the product of F8, is composed of multiple domains designated A1-A2-B-A3-C1-C2. FVIII is known to interact with diverse proteins, and this characteristic may be important for hemostasis. However, little is known about domain-specific functions or their specific binding partners. METHODS: To determine F8 domain-specific functions during blood coagulation, the FVIII domains A1, A2, A3, and C were cloned from Hep3B hepatocytes. Domain-specific recombinant polypeptides were glutathione S-transferase (GST)- or polyhistidine (His)-tagged, over-expressed in bacteria, and purified by specific affinity chromatography. RESULTS: Recombinant polypeptides of predicted sizes were obtained. The GST-tagged A2 polypeptide interacted with coagulation factor IX, which is known to bind the A2 domain of activated FVIII. CONCLUSION: Recombinant, domain-specific polypeptides are useful tools to study the domain-specific functions of FVIII during the coagulation process, and they may be used for production of domain-specific antibodies.


Subject(s)
Antibodies , Bacteria , Blood Coagulation , Chromatography, Affinity , Clone Cells , Factor IX , Factor VIII , Glutathione Transferase , Hemophilia A , Hemostasis , Hepatocytes , Humans , Peptides
16.
Article in English | WPRIM | ID: wpr-13538

ABSTRACT

We are reporting our experience of oral rivaroxaban (Xarelto(R)) treatment for L-asparaginase (L-ASP)-induced deep vein thrombophlebitis in the lower extremity developed during childhood acute lymphoblastic leukemia (ALL) chemotherapy, with a brief review of the literature. A 16-year-old boy was admitted to our institution with right lower leg pain and gait difficulties. He was diagnosed with ALL and started chemotherapy protocol. He had been under a chemotherapy course of delayed intensification (DI)-1. We began antibiotics treatment for possible inflammation including cellulitis of the leg and planned an MRI scan. The MRI scan indicated thrombophlebitis of the right posterior calf deep veins. Subsequent DVT CT and coagulation profiles showed other abnormal findings. Coagulation factor assay were noted with decreased levels of multi factors; Factor II 45%, Factor IX 35.3 %, Factor X 30%, Factor XI 19%, Factor XII 22%, and anti-coagulants levels were decreased also with variant degrees; Protein C Activity 51%, Protein C Ag 54.5%, Protein S Activity 35%, Protein S Antigen, total 27.1%, Protein S Antigen, free 41.7%. Low molecular heparin (LMWH) treatment was initiated and the patient was switched to oral rivaroxaban (Xarelto(R)). After 6 weeks treatment, abnormal coagulation profiles and MRI scan showed improvement. Furthermore, the patient had no other symptoms or recurrence of thrombotic events. There was no significant adverse reaction to rivaroxaban in this patient.


Subject(s)
Adolescent , Anti-Bacterial Agents , Blood Coagulation Factors , Cellulitis , Drug Therapy , Factor IX , Factor X , Factor XI , Factor XII , Gait , Heparin , Humans , Inflammation , Leg , Lower Extremity , Magnetic Resonance Imaging , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Protein C , Protein S , Prothrombin , Recurrence , Thrombophlebitis , Veins , Rivaroxaban
17.
Chinese Journal of Biotechnology ; (12): 492-503, 2014.
Article in Chinese | WPRIM | ID: wpr-279500

ABSTRACT

We established methods to isolate human amniotic fluid-derived progenitor cells (hAFPCs), and analyze the ability of hAFPCs to secrete human coagulation factor IX (hFIX) after gene modification. The hAFPCs were manually isolated by selection for attachment to gelatin coated culture dish. hFIX cDNA was transfected into hAPFCs by using a lentiviral vector. The hFIX protein concentration and activity produced from hAFPCs were determined by enzyme-linked immunosorbent assay (ELISA) and clotting assay. The isolated spindle-shaped cells showed fibroblastoid morphology after three culture passages. The doubling time in culture was 39.05 hours. Immunocytochemistry staining of the fibroblast-like cells from amniotic fluid detected expression of stem cell markers such as SSEA4 and TRA1-60. Quantitative PCR analysis demonstrated the expression of NANOG, OCT4 and SOX2 mRNAs. Transfected hAFPCs could produce and secrete hFIX into the culture medium. The observed concentration of secreted hFIX was 20.37% +/- 2.77% two days after passage, with clotting activity of 16.42% +/- 1.78%. The amount of hFIX:Ag reached a plateau of 50.35% +/- 5.42%, with clotting activity 45.34% +/- 4.67%. In conclusion, this study established method to isolate and culture amniotic fluid progenitor cells. Transfected hAFPCs can produce hFIX at stable levels in vitro, and clotting activity increases with higher hFIX concentration. Genetically engineered hAFPC are a potential method for prenatal treatment of hemophilia B.


Subject(s)
Amniotic Fluid , Cell Biology , Blood Coagulation , Cell Culture Techniques , Cell Separation , Methods , DNA, Complementary , Factor IX , Genetic Engineering , Genetic Vectors , Humans , Stem Cells , Cell Biology , Metabolism , Transfection
18.
Article in Korean | WPRIM | ID: wpr-645907

ABSTRACT

BACKGROUND AND OBJECTIVES: Primary squamous cell carcinoma (SCC) of thyroid is an unusual tumor, accounted for approximately 1.1% of all neoplasms of the thyroid gland. It is highly lethal, like anaplastic thyroid carcinoma, in terms of aggressive clinical behavior. In the literature, the best treatment of this tumor is by surgery and the use of combination therapy that includes postoperative radiation, chemotherapy and radioiodine therapy; however, the effect of treatment is very poor. This study aims to identify the clinical features of SCC of thyroid, and to devise a better treatment method. SUBJECTS AND METHOD: Journals citing SCC of thyroid were identified from Pubmed, Korea Med, and Google and the clinical records reported therewithin from 1990 to 2013 were reviewed. A total of 40 patients were analyzed from 21 well-organized papers by searching the following keywords: squamous cell carcinoma, primary, thyroid, excerpt of the patient's age, sex, clinical features, pathologic findings, therapy, course and prognosis. RESULTS: We analyzed the treatment results of 40 patients from a total of 21 papers. Patients, consisting of 17 men and 23 women, were found in the age range of 24-88, with the mean age of 63.2. The follow-up period ranged from one to 96 months, with the mean being 15 months, and the size of the mass varied from 1 cm to 15 cm. Histopathologically, we found 13 patients with only SCC mixture of SCC and 22 patients with papillary thyroid carcinoma (PTC). Each of the following diseases were identified with one patient: a mixture of SCC and Hashimoto thyroiditis, a mixture of follicular thyroid carcinoma (FTC), SCC and FTC and mixed Hurtle cell cancer, SCC and PTC and mixed Hashimoto thyroiditis, and SCC, PTC with mixed insula cancer. Thirty-two patients underwent total thyroidectomy, and 30 patients underwent total thyroidectomy accompanied by neck dissection. Twelve patients received postoperative radiation therapy, and five patients received postoperative chemotherapy. Nineteen patients were observed without recurrence of the disease, and ten patients were found to be in stage III or less. CONCLUSION: SCC of the thyroid showed aggressive clinical characteristics, however, good results can be expected with early diagnosis and treatment. If tumor is found only within the thyroid, we expect good therapeutic results after the same treatment as PTC.


Subject(s)
Adenocarcinoma, Follicular , Carcinoma , Carcinoma, Squamous Cell , Early Diagnosis , Factor IX , Female , Follow-Up Studies , Hashimoto Disease , Humans , Korea , Male , Neck Dissection , Recurrence , Thyroid Gland , Thyroid Neoplasms , Thyroidectomy
19.
Article in Korean | WPRIM | ID: wpr-645885

ABSTRACT

BACKGROUND AND OBJECTIVES: To identify the relation between the preservation status of the parathyroid glands and the risk of hypoparathyroidism after total thyroidectomy and central lymph node dissection in papillary thyroid carcinoma. SUBJECTS AND METHOD: A retrospective review was carried out for the medical records of 63 patients with papillary thyroid carcinoma (PTC), who satisfied our inclusion criteria and received treatment at the Department of Otolaryngology-Head and Neck Surgery, Hospital from May 2010 to December 2011. Patients with PTC who underwent total thyroidectomy with central lymph node dissection (CLND) were included and grouped according to the number of preserved parathyroid glands as follows: Group 1 (with four intact glands), Group 2 (three intact glands), Group 3 (less than two intact glands). The total and ionized serum calcium and intact parathyroid hormone levels of each group were monitored after the surgery. Patients with postoperative symptomatic hypocalcemia were considered to have postoperative hypoparathyroidism and received calcium/vitamin D therapy. The hypoparathyroidism was considered to be permanent when calcium/vitamin D therapy was still required six months after surgery. RESULTS: Out of 63 cases of total thyroidectomy with CLND, 31 (49.2%) showed postoperative hypoparathyroidism as demonstrated by laboratory findings. Permanent hypoparathyroidism, however, was not observed in these cases. The development of hypoparathyroidism was not significantly related with the number of preserved parathyroid glands. CONCLUSION: To prevent postoperative hypoparathyroidism following total thyroidectomy and CLND, at least two parathyroid glands should be preserved in situ with an intact blood supply in order to prevent permanent hypoparathyroidism after the surgery.


Subject(s)
Calcium , Carcinoma , Factor IX , Humans , Hypocalcemia , Hypoparathyroidism , Lymph Node Excision , Lymph Nodes , Medical Records , Neck , Parathyroid Glands , Parathyroid Hormone , Retrospective Studies , Thyroid Gland , Thyroid Neoplasms , Thyroidectomy
20.
KMJ-Kuwait Medical Journal. 2013; 45 (4): 319-323
in English | IMEMR | ID: emr-139625

ABSTRACT

Acquired childhood multiple clotting factor inhibitors are rare especially in the absence of lupus anticoagulants. They may represent multiple specific inhibitors or may be non-specific, resulting from molecular mimicry or cross-reacting antibodies. Their exact nature and natural history are not well known. To report our experience with seven children presenting with prolonged activated partial thromboplastin time [APTT], with or without bleeding, not corrected by mixing, and showing deficiency of > one clotting factor. Prospective review. Mubarak Hospital, Kuwait. Patients referred to the pediatric hematology unit between 2010 and 2012 with deranged coagulation profiles with or without bleeding, without a previous or family history of a bleeding disorder. They all had multiple clotting factor deficiencies. Prothrombin time [PT] and APTT assay. Control of bleeding and normalization of coagulation factors and APTT. The patients were aged 6 months to 8 years; three presented with mild to moderate bleeding and five had preceding viral infections. Factor IX was decreased in all cases in addition to deficiencies of factors VIII, X and / or XI in various combinations. There was spontaneous recovery in five patients in whom the factors and APTT normalized within two to five months. One patient died from massive pulmonary hemorrhage and another with nephropathy remains the same after two years. Multiple acquired inhibitors are not uncommon in children, tend to follow viral infections, and are usually transient and not associated with severe bleeding


Subject(s)
Humans , Female , Lymphatic Diseases/diagnosis , Hemorrhage/pathology , Thromboplastin , Factor IX , Partial Thromboplastin Time , Review Literature as Topic
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