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1.
BMC Med Genet ; 19(1): 15, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29368589

RESUMO

BACKGROUND: Preimplantation genetic diagnosis (PGD) is a powerful tool for preventing the transmission of Mendelian disorders from generation to generation. However, PGD only can identify monogenically inherited diseases, but not other potential monogenic pathologies. We aimed to use PGD to deliver a healthy baby without congenital FVII deficiency or other common Mendelian diseases in a couple in which both individuals carried a deleterious mutation in the F7 gene. METHODS: After both members of the couple were confirmed to be carriers of the F7 gene mutation by Sanger sequencing, expanded carrier screening (ECS) for 623 recessive inheritance diseases was performed to detect pathological mutations in other genes. PGD and preimplantational genetic screening (PGS) were employed to exclude monogenic disorders and aneuploidy for their embryos. RESULTS: ECS using targeted capture sequencing technology revealed that the couple carried the heterozygous disease-causative mutations c.3659C > T (p.Thr1220Ile) and c.3209G > A (p.Arg1070Gln) in the CFTR gene. After PGD and PGS, one of their embryos that was free of congenital FVII deficiency, cystic fibrosis (CF) and aneuploidy was transferred, resulting in the birth of a healthy 3200 g male infant. CONCLUSION: We successfully implemented PGD for congenital FVII deficiency and PGD after ECS to exclude CF for the first time to the best of our knowledge. Our work significantly improved the reproductive outcome for the couple and provides a clear example of the use of ECS combined with PGD to avoid the delivery of offspring affected not only by identified monogenically inherited diseases but also by other potential monogenic pathologies and aneuploidy.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Deficiência do Fator VII/diagnóstico , Deficiência do Fator VII/genética , Testes Genéticos , Diagnóstico Pré-Implantação , Aneuploidia , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Fibrose Cística/prevenção & controle , Fator VII/genética , Fator VII/metabolismo , Deficiência do Fator VII/prevenção & controle , Feminino , Fertilização in vitro , Deleção de Genes , Genes Recessivos , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/prevenção & controle , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Linhagem , Gravidez , Resultado da Gravidez , Análise de Sequência de DNA , Sequenciamento Completo do Genoma
2.
Blood Cells Mol Dis ; 67: 86-90, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28038846

RESUMO

Severe congenital factor VII (FVII) deficiency is a rare bleeding disorder. Prophylaxis with replacement therapy has been suggested to patients, yet the most beneficial dosing regimens and therapy intervals are still to be defined. Due to the lack of evidence-based data, we hereby present our experience with long-term administration and monitoring primary prophylaxis in children with severe FVII deficiency and an extremely high bleeding risk. Four children with familial FVII deficiency, treated by prophylactic recombinant activated factor VII (rFVIIa), 15-30µg/kg/dose, given 2-3 times weekly since infancy, are discussed. Clinical follow up and monitoring laboratory assays, including thrombin generation, measured at various time points after prophylactic rFVIIa administration are presented. Among our treated patients neither FVII activity nor thrombin generation parameters (both already declined 24h post rFVIIa administration) were able to predict the impact of prophylaxis, and could not be used as surrogate markers in order to assess the most beneficial treatment frequency. However, the long clinical follow-up and comprehensive laboratory assessment performed, have shown that early primary prophylaxis as administered in our cohort was safe and effective.


Assuntos
Deficiência do Fator VII/prevenção & controle , Fator VIIa/uso terapêutico , Criança , Pré-Escolar , Deficiência do Fator VII/sangue , Deficiência do Fator VII/complicações , Deficiência do Fator VII/metabolismo , Fator VIIa/administração & dosagem , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/metabolismo , Hemorragia/prevenção & controle , Humanos , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Trombina/metabolismo
3.
Haemophilia ; 21(6): 812-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25952977

RESUMO

INTRODUCTION: The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. AIMS: We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. METHODS: Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. RESULTS: The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pdFVII) or 20-30mcg/kg (rFVIIa) twice or three times/weeks was described to be effective. CONCLUSIONS: In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pdFVII) or 20-30 microg/kg (rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis.


Assuntos
Deficiência do Fator VII/prevenção & controle , Fator VIIa/farmacologia , Adolescente , Adulto , Criança , Pré-Escolar , Deficiência do Fator VII/complicações , Deficiência do Fator VII/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Recombinantes/farmacologia , Fatores de Tempo , Adulto Jovem
4.
Haematologica ; 98(4): 538-44, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23403322

RESUMO

Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (<1-45 years of age, 21 female). Severest phenotypes (central nervous system, gastrointestinal, joint bleeding episodes) were highly prevalent. Twenty-one patients received recombinant activated factor VII (24 courses), four received plasma-derived factor VII, and ten received fresh frozen plasma. Prophylactic schedules clustered into "frequent" courses (three times weekly, n=23) and "infrequent" courses (≤ 2 times weekly, n=15). Excluding courses for menorrhagia, "frequent" and "infrequent" courses produced 18/23 (78%) and 5/12 (41%) "excellent" outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on "frequent" administrations (three times weekly) and a 90 µg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency.


Assuntos
Deficiência do Fator VII/prevenção & controle , Fator VII/uso terapêutico , Fator VIIa/uso terapêutico , Plasma , Adolescente , Adulto , Criança , Pré-Escolar , Fator VIIa/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Cleft Palate Craniofac J ; 43(1): 108-11, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16405366

RESUMO

The association between factor VII deficiency and cleft palate has never been described. The case of a child with cleft palate and factor VII deficiency who successfully underwent palatoplasty is described in this article. To allow surgical treatment, through maintenance of a normal prothrombin time, the patient was given 15 microg/kg of recombinant factor VIIa every 12 hours, starting 20 minutes before surgery and ending the third postoperative day. No abnormal perioperative bleeding was observed. Use of recombinant factor VIIa in bleeding prophylaxis or treatment is widespread. Doses are much higher in these cases. The reduction of dosage allows easier administration, especially in pediatric patients, without affecting drug efficacy.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Fissura Palatina/cirurgia , Deficiência do Fator VII/prevenção & controle , Pré-Medicação , Pré-Escolar , Coagulantes/administração & dosagem , Coagulantes/uso terapêutico , Fator VIIa/administração & dosagem , Fator VIIa/uso terapêutico , Humanos , Masculino , Palato/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Tempo de Protrombina , Proteínas Recombinantes , Procedimentos de Cirurgia Plástica
7.
Haemophilia ; 10(3): 295-8, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15086331

RESUMO

Use of recombinant factor VIIa (rFVIIa, NovoSeven in patients with congenital FVII deficiency has been reported for the prophylactic management of surgical bleeding and for the treatment of acute bleeding episodes. Because of its short half-life, the use of rFVIIa on a regular prophylactic regimen has not been routinely adopted. In this report, we describe our successful experience with rFVIIa prophylaxis in preventing recurrent target joint bleeding in a severely FVII-deficient adolescent.


Assuntos
Deficiência do Fator VII/prevenção & controle , Fator VII/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Adolescente , Deficiência do Fator VII/congênito , Fator VIIa , Hemartrose/etiologia , Hemartrose/prevenção & controle , Humanos , Masculino
8.
Gynecol Obstet Invest ; 50(4): 275-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11093053

RESUMO

This paper reports a case of factor VII deficiency, a very rare autosomal recessive disorder, in a primipara at 37 weeks of gestation in whom we administered prophylactic therapy with factor VII every 12 h until 24 h after delivery. The prophylactic use of factor VII enabled the woman to deliver without hemorrhagic complications.


Assuntos
Deficiência do Fator VII/tratamento farmacológico , Fator VII/administração & dosagem , Complicações Hematológicas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Adulto , Deficiência do Fator VII/diagnóstico , Deficiência do Fator VII/prevenção & controle , Feminino , Seguimentos , Humanos , Gravidez , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/prevenção & controle , Terceiro Trimestre da Gravidez , Gravidez de Alto Risco , Índice de Gravidade de Doença
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