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1.
Br J Haematol ; 200(3): 344-352, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36229963

RESUMEN

Congenital factor VII (FVII) deficiency is a rare bleeding disorder characterised by a wide molecular and clinical heterogeneity. We investigated the clinical phenotype of 193 patients and F7 genotype of 55/193 patients with FVII deficiency throughout China and showed their current status of management. The most frequent bleeding symptoms were epistaxis (44.6%), cutaneous (38.9%), oral cavity (40.4%) bleeding and menorrhagia (44.3% of females of reproductive age). Fatal central nervous system bleeding and disabling joint bleeding occurred in three patients each. The majority of patients (89.6%) had FVII activity (FVII:C) ≤10% and the proportion of symptomatic patients in this group (79.8%) was significantly higher than that in the groups with FVII:C >10%-25% (41.7%) and >25%-50% (37.5%) (χ2 = 13.641, p = 0.001). Major bleeds occurred only in patients with FVII:C ≤10%. In total 55 patients underwent genotype analysis: most variants were missense (62.5%) and most patients had homozygous/compound heterozygous (85.4%) variants. Prothrombin complex concentrates (72.4%) were the most frequently used on-demand replacement therapy. Prophylaxis before delivery decreased the risk of postpartum bleeding in women (χ2 = 69.243, p = 0.000). Our study provides useful information on the phenotype, genotype and current status of FVII-deficiency patients management and may promote further exploration and care of this population in the future.


Asunto(s)
Deficiencia del Factor VII , Humanos , Femenino , Deficiencia del Factor VII/genética , Deficiencia del Factor VII/terapia , Genotipo , Factor VII/genética , Fenotipo , Homocigoto , Hemorragia/genética , Hemorragia/prevención & control
3.
Haematologica ; 105(3): 829-837, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31273093

RESUMEN

Despite the exhaustive screening of F7 gene exons and exon-intron boundaries and promoter region, a significant proportion of mutated alleles remains unidentified in patients with coagulation factor VII deficiency. Here, we applied next-generation sequencing to 13 FVII-deficient patients displaying genotype-phenotype discrepancies upon conventional sequencing, and identified six rare intronic variants. Computational analysis predicted splicing effects for three of them, which would strengthen (c.571+78G>A; c.806-329G>A) or create (c.572-392C>G) intronic 5' splice sites (5'ss). In F7 minigene assays, the c.806-329G>A was ineffective while the c.571+78G>A change led to usage of the +79 cryptic 5'ss with only trace levels of correct transcripts (3% of wild-type), in accordance with factor VII activity levels in homozygotes (1-3% of normal). The c.572-392C>G change led to pseudo-exonization and frame-shift, but also substantial levels of correct transcripts (approx. 70%). However, this variant was associated with the common F7 polymorphic haplotype, predicted to further decrease factor VII levels; this provided some kind of explanation for the 10% factor VII levels in the homozygous patient. Intriguingly, the effect of the c.571+78G>A and c.572-392C>G changes, and particularly of the former (the most severe and well-represented in our cohort), was counteracted by antisense U7snRNA variants targeting the intronic 5'ss, thus demonstrating their pathogenic role. In conclusion, the combination of next-generation sequencing of the entire F7 gene with the minigene expression studies elucidated the molecular bases of factor VII deficiency in 10 of 13 patients, thus improving diagnosis and genetic counseling. It also provided a potential therapeutic approach based on antisense molecules that has been successfully exploited in other disorders.


Asunto(s)
Deficiencia del Factor VII , Exones , Factor VII/genética , Factor VII/metabolismo , Deficiencia del Factor VII/diagnóstico , Deficiencia del Factor VII/genética , Deficiencia del Factor VII/terapia , Secuenciación de Nucleótidos de Alto Rendimiento , Homocigoto , Humanos , Mutación , Empalme del ARN
4.
Hematology ; 24(1): 97-102, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30191763

RESUMEN

OBJECTIVE: Factor VII deficiency is the commonest of the rare bleeding disorders with limited knowledge on clinical profile. The objective of this study was to study the prevalence and clinico-hematological profile of factor VII-deficient patients. METHODS: It is a retrospective observational study of probable inherited factor VII deficiency covering 18 months. Their clinical profile, family history, investigation and treatment records were studied in detail. RESULTS: The study group comprised of total 12 factor VII deficiency cases with mean age of 17.5 years of onset of symptoms. The commonest symptom was menorrhagia (41.6%) followed by epistaxis (25%) and easy bruisability (16.6%). These 12 patients when categorized according to bleeding severity: severe bleeding - 2, moderate bleeding - 3, mild bleeding - 6 and asymptomatic - 1. All cases had prolonged prothrombin time (PT) with mean PT of 35.4 seconds (range 18-50 seconds) and mean prolongation of PT from upper limit of normal - 19.4 seconds (range 2-34 seconds). Factor VII levels ranged from < 1-40% in these patients. Clinical symptoms were not in concordance with factor levels. Of 12 patients, required treatment other than local measures. DISCUSSION AND CONCLUSION: Inherited factor VII deficiency is the commonest autosomally inherited factor deficiency with marked variation in the age of presentation and clinical symptoms. The laboratory results in form of PT and factor VII levels do not correlate with the severity of clinical presentation. A comprehensive evaluation to exclude acquired causes of factor VII deficiency, e.g. obesity, liver diseases, vitamin K deficiency and acquired inhibitors is required before labeling it as inherited in the absence of family history and molecular studies.


Asunto(s)
Deficiencia del Factor VII/sangre , Factor VIII/metabolismo , Hemorragia/sangre , Adolescente , Adulto , Anciano , Niño , Preescolar , Deficiencia del Factor VII/terapia , Femenino , Hemorragia/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
Artículo en Español | LILACS | ID: biblio-1013825

RESUMEN

RESUMEN No hay guías específicas para el manejo de pacientes embarazadas con la deficiencia de Factor VII; no hay una correlación entre el nivel de FVII y el riesgo de hemorragia y el nivel del Factor VII aumento durante el embarazo. Presentamos un caso clínico, el manejo y las recomendaciones del consenso.


Asunto(s)
Humanos , Femenino , Embarazo , Adulto Joven , Complicaciones Hematológicas del Embarazo/diagnóstico , Deficiencia del Factor VII/diagnóstico , Complicaciones Hematológicas del Embarazo/terapia , Transfusión Sanguínea , Resultado del Embarazo , Cesárea , Deficiencia del Factor VII/congénito , Deficiencia del Factor VII/terapia , Hemorragia/etiología
6.
Pan Afr Med J ; 31: 156, 2018.
Artículo en Francés | MEDLINE | ID: mdl-31065316

RESUMEN

Factor VII deficiency is rare, with an estimated prevalence rate of 1/1,000,000. It is transmitted as an autosomal recessive trait. It can cause simple nosebleeds up to cerebral hemorrhage. Our study aims to focus on the clinical features and the importance of screening in patients with this rare deficit. We report the cases of two brothers with this deficit. Child aged 8 years, born to non-consanguineous marriage who was the youngest of two children. He had a history of post-circumcision bleeding and was admitted to our Department for the treatment of recurrent nosebleeds occurred over the last 4 years. Screening tests of hemostasis showed low Prothrombin (PT), normal Activated thromboplastin time (ATT), while factor assay revealed factor VII deficiency with a rate of 26%. The patient underwent spaced fresh frozen plasma (FFP) transfusions due to nosebleeds and wounds. Family screening was not performed. The eldest brother, aged 11 years, presented with very abundant nosebleeds. Somatic examination was unremarkable. Given his history, the patient underwent factor VII assay revealing a rate of 55% and parent screening was scheduled. The diagnosis of congenital factor VII deficiency in a patient motivates family screening in order to perform screening tests in other carriers of factor VII deficiency. This would avoid severe manifestations, even fatal, considering that studies have not shown a correlation between factor VII rate and the severity of patient's status.


Asunto(s)
Epistaxis/etiología , Deficiencia del Factor VII/diagnóstico , Tamizaje Masivo/métodos , Transfusión de Componentes Sanguíneos/métodos , Niño , Deficiencia del Factor VII/congénito , Deficiencia del Factor VII/terapia , Humanos , Masculino , Plasma , Recurrencia , Índice de Severidad de la Enfermedad
7.
Hematology ; 22(6): 375-379, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28176610

RESUMEN

OBJECTIVES: To determine whether heterozygotes with FVII deficiency have a bleeding tendency or not. PATIENTS AND METHODS: Eighty-four patients (OK) heterozygous for FVII deficiency, at the onset of the study, were paired with unaffected family members and followed for a long period of time (mean 22.6 years) for the occurrence of bleeding. Diagnosis of heterozygosis had to be based on family studies, clotting, immunological assays and genetic analysis. RESULTS: The mean FVII activity level was 0.51 IU/dl (range 35-65) and 94 IU/dl (range 88-118) in the heterozygotes and in the normal counterparts, respectively. Documented bleeding manifestations occurred in eight heterozygotes and in seven normal subjects. Statistical analysis of the difference was not significant. Bleeding manifestations were easy bruising, bleeding after tooth extractions, menorrhagia, epistaxis with no difference among the two groups. There was no strict correlation between bleeding and FVII activity levels. CONCLUSIONS: The study indicates that heterozygotes for FVII deficiency show rare bleeding manifestations which are also present in the unaffected family members with normal FVII levels. This indicates that Factor VII activity levels played no role in the occurrence of the bleeding symptoms. Furthermore, FVII levels of around 0.40 IU/dl are capable of assuring a normal hemostasis.


Asunto(s)
Deficiencia del Factor VII/complicaciones , Deficiencia del Factor VII/genética , Factor VII/genética , Hemorragia/diagnóstico , Hemorragia/etiología , Heterocigoto , Mutación , Adolescente , Adulto , Pruebas de Coagulación Sanguínea , Activación Enzimática , Deficiencia del Factor VII/terapia , Familia , Femenino , Humanos , Masculino , Fenotipo , Valores de Referencia , Adulto Joven
9.
Blood Coagul Fibrinolysis ; 28(6): 490-492, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27306331

RESUMEN

: Severe hereditary factor VII deficiency is a rare bleeding disorder and may be associated with a severe bleeding phenotype. We describe a pregnancy in a 33-year-old woman with compound heterozygous factor VII deficiency and a history of severe menorrhagia and mucocutaneous bleedings. After discontinuation of contraceptives, menstruation was covered with recombinant activated factor VII (rFVIIa), and during pregnancy, rFVIIa had to be administered in first trimester in doses ranging from 15 to 90 µg/kg per day because of recurrent retroplacental hematomas and vaginal bleedings. Thrombin generation was measured in first trimester at different doses of rFVIIa and showed an increase in lag time when doses of less than 30 µg/kg/day were administered, whereas time to thrombin peak and peak thrombin were not influenced. A low-dose rFVIIa prophylactic treatment of 15 µg/kg every other day in the late second and in the third trimester was sufficient to allow a successful childbirth in this patient with severe factor VII deficiency.


Asunto(s)
Deficiencia del Factor VII/terapia , Resultado del Embarazo , Adulto , Factor VIIa/administración & dosificación , Femenino , Humanos , Nacimiento Vivo , Embarazo , Complicaciones Hematológicas del Embarazo/terapia , Premedicación/métodos , Proteínas Recombinantes/administración & dosificación
10.
Clin Appl Thromb Hemost ; 23(7): 703-710, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27701084

RESUMEN

Factor VII (FVII) deficiency is a rare inheritable bleeding disorder affecting 1/500 000 individuals. Clinical manifestations are heterogeneous, from asymptomatic to severe and potentially fatal bleeding. These clinical manifestations do not correlate well with FVII plasma levels. For this reason, FVII-deficient patient management during surgery or for long-term prophylaxis remains challenging. Laboratory testing for FVII activity is, however, the first-line method for FVII deficiency diagnosis and is helpful for managing patients in combination with clinical history. Additional testing consists of FVII immunoassay and genetic testing. Genetic abnormalities on the FVII gene are heterogeneous and can translate into quantitative or qualitative defects. Some of the latter can react differently with different thromboplastins; this can be misleading for the laboratory as no consensus exists at present on an FVII deficiency diagnosis methodology. Indeed, no single test is able to predict accurately the bleeding risk. This review provides a broad picture of inherited and acquired FVII deficiency with a particular focus on laboratory diagnosis.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Deficiencia del Factor VII/diagnóstico , Manejo de la Enfermedad , Deficiencia del Factor VII/terapia , Humanos
11.
Haemophilia ; 22(5): e417-22, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27501477

RESUMEN

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.


Asunto(s)
Deficiencia del Factor VII/terapia , Factor VII/uso terapéutico , Hemorragias Intracraneales/prevención & control , Trasplante de Hígado , Proteínas Recombinantes/uso terapéutico , Preescolar , Deficiencia del Factor VII/complicaciones , Femenino , Humanos , Lactante , Recién Nacido , Hemorragias Intracraneales/etiología
12.
Sci Rep ; 6: 28304, 2016 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-27341548

RESUMEN

Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.


Asunto(s)
Deficiencia del Factor VII/terapia , Factor VII/genética , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Transcripción Genética , Secuencia de Bases , Sitios de Unión , Factor VII/metabolismo , Deficiencia del Factor VII/genética , Deficiencia del Factor VII/metabolismo , Genes Reporteros , Terapia Genética , Células HEK293 , Células Hep G2 , Hepatocitos/metabolismo , Humanos , Luciferasas de Luciérnaga/biosíntesis , Luciferasas de Luciérnaga/genética , Mutación , Ingeniería de Proteínas , Proteínas Recombinantes de Fusión , Activación Transcripcional
13.
Thromb Res ; 141: 22-7, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26962982

RESUMEN

While the immune response to hemophilic factors in hemophilia has been widely studied, little is known about the development of anti-Factor VII (FVII) antibodies in FVII deficiency. We developed a robust technique based on the x-MAP technology to detect the presence of antibodies against FVII and characterize their isotype and validated this method using blood samples from 100 patients with FVII deficiency (median FVII clotting activity [FVII:C]: 6%) and 95 healthy controls. Anti-FVII antibodies were detected in patients but also in some controls, although the concentration of total immunoglobulin G (IgGt) and IgG1 and IgG4 subclasses was significantly different between groups. The IgG1 subclass concentrations remained significantly different also when only untreated patients were compared with controls. This difference could partially be related to the F7 genotype, particularly in patients harboring the p.Arg139Gln mutation. This x-MAP-based method might be useful for assessing the immunogenicity of novel FVII compounds and of activated FVII (FVIIa) concentrates. Further prospective studies are needed to better understand the clinical relevance of these antibodies in the management of patients with FVII deficiency.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Deficiencia del Factor VII/inmunología , Deficiencia del Factor VII/terapia , Factor VII/inmunología , Factor VIIa/inmunología , Factor VIIa/uso terapéutico , Inmunoglobulina G/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Niño , Preescolar , Estudios de Cohortes , Deficiencia del Factor VII/sangre , Femenino , Humanos , Inmunoensayo/métodos , Inmunoglobulina G/sangre , Lactante , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/uso terapéutico , Adulto Joven
14.
Blood Cells Mol Dis ; 57: 8-12, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26852649

RESUMEN

BACKGROUND: In congenital Factor (F) VII deficiency bleeding phenotype and intrinsic FVII activity levels don't always correlate. Patients with FVII activity levels <30% appear to have a higher bleeding propensity, but bleeding can also occur at higher FVII activity levels. Reasons for bleeding at higher FVII activity levels are unknown, and it remains challenging to manage such patients clinically. CASE: A 19year old male with spontaneous intracranial hemorrhage and FVII activity levels of 44%, requiring emergent surgical intervention and a strategy for FVII replacement. Genotyping showed the rare heterozygous FVII 9729del4 mutation. Bleed evacuation was complicated by epidural abscess requiring craniectomy, bone graft procedures, and prolonged administration of recombinant human (rh) activated FVII (FVIIa). The patient recovered without neurological deficits, and remains on prophylactic low dose treatment with rhFVIIa in relation to risky athletic activities. CONCLUSION: For clinicians, it is important to recognize that effects of rhFVIIa within these pathways are independent of its contribution to blood clot formation and cannot be assessed by clotting assays. Reduced FVII levels should therefore not be dismissed, as even a mild reduction may result in spontaneous bleeding. Treatment of mild FVII deficiency requires a careful case-by-case approach, based on the clinical scenario.


Asunto(s)
Secuencia de Bases , Hemorragia Cerebral/genética , Absceso Epidural/genética , Deficiencia del Factor VII/genética , Factor VII/genética , Eliminación de Secuencia , Trasplante Óseo , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/patología , Hemorragia Cerebral/terapia , Análisis Mutacional de ADN , Craniectomía Descompresiva , Absceso Epidural/complicaciones , Absceso Epidural/patología , Absceso Epidural/terapia , Deficiencia del Factor VII/complicaciones , Deficiencia del Factor VII/patología , Deficiencia del Factor VII/terapia , Factor VIIa/uso terapéutico , Expresión Génica , Heterocigoto , Humanos , Masculino , Datos de Secuencia Molecular , Proteínas Recombinantes/uso terapéutico , Adulto Joven
15.
Acta Clin Belg ; 71(2): 63-70, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26400474

RESUMEN

OBJECTIVES: Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. METHODS: We performed a literature search and included all articles published between 1980 and August 2015. RESULTS AND CONCLUSIONS: Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.


Asunto(s)
Deficiencia del Factor VII , Deficiencia del Factor VII/complicaciones , Deficiencia del Factor VII/diagnóstico , Deficiencia del Factor VII/fisiopatología , Deficiencia del Factor VII/terapia , Factor VIIa/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Hemorragia/etiología , Humanos , Infecciones/complicaciones , Masculino , Neoplasias/complicaciones , Pronóstico , Vitamina K/uso terapéutico
16.
Blood ; 127(5): 565-71, 2016 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-26702064

RESUMEN

Factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder treated by infusion of fresh-frozen plasma, plasma-derived FVII concentrates and low-dose recombinant activated FVII. Clinical data suggest that a mild elevation of plasma FVII levels (>10% normal) results in improved hemostasis. Research dogs with a G96E missense FVII mutation (FVII-G96E) have <1% FVII activity. By western blot, we show that they have undetectable plasmatic antigen, thus representing the most prevalent type of human FVII deficiency (low antigen/activity). In these dogs, we determine the feasibility of a gene therapy approach using liver-directed, adeno-associated viral (AAV) serotype 8 vector delivery of a canine FVII (cFVII) zymogen transgene. FVII-G96E dogs received escalating AAV doses (2E11 to 4.95E13 vector genomes [vg] per kg). Clinically therapeutic expression (15% normal) was attained with as low as 6E11 vg/kg of AAV and has been stable for >1 year (ongoing) without antibody formation to the cFVII transgene. Sustained and supraphysiological expression of 770% normal was observed using 4.95E13 vg/kg of AAV (2.6 years, ongoing). No evidence of pathological activation of coagulation or detrimental animal physiology was observed as platelet counts, d-dimer, fibrinogen levels, and serum chemistries remained normal in all dogs (cumulative 6.4 years). We observed a transient and noninhibitory immunoglobulin G class 2 response against cFVII only in the dog receiving the highest AAV dose. In conclusion, in the only large-animal model representing the majority of FVII mutation types, our data are first to demonstrate the feasibility, safety, and long-term duration of AAV-mediated correction of FVII deficiency.


Asunto(s)
Deficiencia del Factor VII/genética , Deficiencia del Factor VII/terapia , Factor VII/genética , Terapia Genética , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Precursores de Proteínas/genética , Adenoviridae/genética , Animales , Perros , Deficiencia del Factor VII/sangre , Expresión Génica , Vectores Genéticos/administración & dosificación , Células HEK293 , Humanos , Mutación Puntual , Transgenes
19.
Injury ; 46(6): 1178-82, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25733368

RESUMEN

Traumatic hemipelvectomy is a lethal catastrophic injury. The reported average age of individuals surviving this trauma is 21 years old, suggesting the necessity of good physiological reserves to survive this type of injury. Dealing with this injury in children may call for special requirements throughout all the stages of diagnosis, treatment and rehabilitation. Experience in the resuscitation and subsequent treatment of individuals suffering from this traumatic condition in the paediatric population is even scarce. There are only several reported cases involving children and none of the paediatric cases suffered from comorbidities prior to their traumatic injury. The present report describes the successful management of a 16-month-old child with a medical history of a rare bleeding disorder a severe coagulation Factor VII deficiency who underwent right-sided traumatic hemipelvectomy.


Asunto(s)
Deficiencia del Factor VII/complicaciones , Hemipelvectomía , Traumatismo Múltiple/cirugía , Huesos Pélvicos/lesiones , Accidentes de Tránsito , Comorbilidad , Deficiencia del Factor VII/terapia , Estudios de Seguimiento , Hemipelvectomía/métodos , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Traumatismo Múltiple/complicaciones , Resultado del Tratamiento
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