ABSTRACT
BACKGROUND: Rational design of synthetic phage-displayed libraries requires the identification of the most appropriate positions for randomization using defined amino acid sets to recapitulate the natural occurrence. The present study uses position-specific scoring matrixes (PSSMs) for identifying and randomizing Camelidae nanobody (VHH) CDR3. The functionality of a synthetic VHH repertoire designed by this method was tested for discovering new VHH binders to recombinant coagulation factor VII (rfVII). METHODS: Based on PSSM analysis, the CDR3 of cAbBCII10 VHH framework was identified, and a set of amino acids for the substitution of each PSSM-CDR3 position was defined. Using the Rosetta design SwiftLib tool, the final repertoire was back-translated to a degenerate nucleotide sequence. A synthetic phage-displayed library was constructed based on this repertoire and screened for anti-rfVII binders. RESULTS: A synthetic phage-displayed VHH library with 1 × 108 variants was constructed. Three VHH binders to rfVII were isolated from this library with estimated dissociation constants (KD) of 1 × 10-8 M, 5.8 × 10-8 M and 2.6 × 10-7 M. CONCLUSION: PSSM analysis is a simple and efficient way to design synthetic phage-displayed libraries.
Subject(s)
Computational Biology , Peptide Library , Single-Domain Antibodies , Single-Domain Antibodies/genetics , Single-Domain Antibodies/chemistry , Single-Domain Antibodies/immunology , Animals , Camelidae/genetics , Camelidae/immunology , Factor VII/genetics , Factor VII/chemistry , Factor VII/immunology , Recombinant Proteins/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Amino Acid SequenceABSTRACT
Congenital factor VII (FVII) deficiency is a rare genetic bleeding disorder characterized by deficient or reduced activity of coagulation FVII. It is caused by genetic variants in the F7 gene. We aimed to evaluate the rate of detection of pathogenic variants in the F7 gene in a large group of patients with FVII deficiency and investigate the correlations between the F7 genotype and FVII activity (FVII:C). Moreover, the influence of the common genetic variant rs6046: c.1238G>A; p.(Arg413Gln), designated as the M2 allele, on FVII:C was investigated. Genetic analysis of the F7 gene was performed on 704 index patients (IPs) using either direct Sanger- or next-generation sequencing. Genetic variants were detected in 390 IPs, yielding a variant detection rate (VDR) of 55%. Notably, the VDR exhibited a linear decline with increasing FVII:C levels. We identified 124 genetic variants, of which 48 were not previously reported. Overall, the frequency of the M2 allele was considerably higher in patients with mild deficiency (FVII:C > 20 IU/dl). Furthermore, IPs lacking an identified pathogenic variant exhibited a significantly higher prevalence of the M2 allele (69%) compared to IPs with a disease-causing variant (47%). These results strongly support the association of the M2 allele with decreased FVII:C levels. This study shows the utility of FVII:C as a predictive marker for identifying pathogenic variants in patients with FVII deficiency. The M2 allele contributes to the reduction of FVII:C levels, particularly in cases of mild deficiency.
Subject(s)
Factor VII Deficiency , Humans , Factor VII Deficiency/genetics , Mutation , Phenotype , Factor VII/genetics , GenotypeABSTRACT
OBJECTIVE: To analyze the types of genetic variants and clinical characteristics of three Chinese pedigrees affected with Hereditary coagulation factor â ¦ (Fâ ¦) deficiency. METHODS: Three pedigrees who had visited the First Affiliated Hospital of Wenzhou Medical University between December 2021 and October 2022 were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT) and Fâ ¦ activity (Fâ ¦:C) were measured in the three probands and their pedigree members. All exons and their flanking sequences were analyzed by direct sequencing, and candidate variants were verified by reverse sequencing. The corresponding variant loci in the family members were also analyzed. ClustalX-2.1-win was used to analyze the conservation of the variant loci. Varcards and Spcards online software was used to predict the pathogenicity of the variants. Pymol software was used to analyze the changes in protein structure and molecular forces. RESULTS: Three cases of hereditary Fâ ¦ deficiency were found to have decreased Fâ ¦:C, prolonged PT and normal APTT. Genetic analysis identified a total of four genetic variants, and all three probands had harbored compound heterozygous variants of the F7 gene, including p.Cys389Gly and p.His408Gln in proband 1, p.Cys389Gly and IVS6+1G>T in proband 2, and IVS6+1G>T and IVS1a+5G>A in proband 3. Conservation analysis showed that both the p.Cys389 and p.His408 loci are highly conserved among orthologous species. Analysis with Varcards and Spcards software showed that these variants were pathogenic. Protein modeling analysis showed that the p.Cys389Gly and p.His408Gln variants may result in altered protein structures and changes in hydrogen bonds. CONCLUSION: The clinical manifestations of the three Fâ ¦-deficient probands may be attributed to the compound heterozygous variants of p.Cys389Gly/p.His408Gln, p.Cys389Gly/IVS6+1G>T and IVS6+1G>T/IVS1a+5G>A of the F7 gene. The combination of the three compound heterozygous variants was unreported previously.
Subject(s)
Factor VII Deficiency , Humans , Pedigree , Heterozygote , Factor VII Deficiency/genetics , Mutation , Factor VII/genetics , ChinaSubject(s)
Factor VII Deficiency , Factor VII , Humans , Factor VII Deficiency/genetics , Taiwan , Male , Female , Factor VII/genetics , Adult , Middle Aged , Mutation , Adolescent , Child , Child, Preschool , Young AdultABSTRACT
BACKGROUND: Synonymous variants are non-pathogenic due to non-substitution of amino acids. However, synonymous exonic terminal nucleotide substitutions may affect splicing. Splicing variants are easily analyzed at RNA level for genes expressed in blood cells. Minigene analysis provides another method for splicing variant analysis of genes that are poorly or not expressed in peripheral blood. METHODS: Whole exome sequencing was performed to screen for potential pathogenic mutations in the proband, which were validated within the family by Sanger sequencing. The pathogenicity of the synonymous mutation was analyzed using the minigene technology. RESULTS: The proband harbored the compound heterogeneous variants c. [291G >A; 572-50C >T] and c.681 + 1G >T in F7, of which the synonymous variant c.291G >A was located at the terminal position of exon 3. Minigene analysis revealed exon3 skipping due to this mutation, which may have subsequently affected protein sequence, structure, and function. CONCLUSION: Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.
Subject(s)
Exons , Factor VII , RNA Splicing , Silent Mutation , Adult , Female , Humans , Male , Pedigree , Factor VII/geneticsABSTRACT
OBJECTIVE: To identify the genetic mutation of coagulation factor â ¦ ( F7) gene in a pedigree with coagulation factor â ¦ (Fâ ¦) deficiency and explore the molecular pathogenesis. METHODS: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (DD), fibrin degradation products (FDP) and coagulation factor â ¦ activity (Fâ ¦:C) of the proband and her family members were detected by Sysmex-CS5100 analyzer. All exons and exon-intron boundaries of the F7 gene were amplified by PCR followed by direct sequencing. The detected mutation was confirmed by reverse sequencing. The ClustalW software was used to analyze the conservatism of the mutant site. Pathogenicity of the mutation was assessed with Mutation Taster and PolyPhen-2 online bioinformatics software. Structure of the mutant protein was analyzed using Swiss-PdbViewer software. RESULTS: The results of routine coagulation tests showed that PT of the proband was markedly extended to 42.5 s, and her Fâ ¦:C significantly reduced to 2%. The Fâ ¦:C of her grandmother, mother and sister had slightly reduced to 49%, 51%, and 42%, respectively. These coagulant parameters of her father were within the normal range. Genetic analysis reveled a heterozygous G>A change at cDNA 646 in exon 6 of F7 gene in the proband, resulting in a replacement of glycine at 156 of Fâ ¦ catalytic region with serine (p.Gly156Ser). The sequencing results of other exons and exon-intron boundaries of her F7 gene were normal. The proband's grandmother, mother and sister were all the carriers of this missense mutation except her father. Bioinformatics analysis showed that the p.Gly156Ser mutation caused polarity change of the amino acid at this site and formation of side chains, leading to increase of protein instability, which may affect catalytic activity of structural domain. Meanwhile, both Mutation Taster and PolyPhen-2 online bioinformatics software also predicted the pathogenicity of this missense mutation with high scores. CONCLUSION: The heterozygous p.Gly156Ser mutation is the direct cause of the reduced Fâ ¦ in this proband.
Subject(s)
Factor VII Deficiency , Factor VII , Mutation , Pedigree , Humans , Female , Factor VII/genetics , Factor VII Deficiency/genetics , Exons , Heterozygote , MaleABSTRACT
Hereditary coagulation factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder. The aims of this study were to identify and verify the pathogenic mutation sites in a family with hereditary coagulation FVII deficiency, and preliminarily explore the underlying mechanisms. We identified a novel combination of compound heterozygous mutations, c.572-1G>A and c.1037A>C in F7 gene, associated with FVII deficiency. The splice site mutation c.572-1G>A led to a truncation, resulting in the loss of the essential catalytic domain of the FVII protein. The c.1037A>C missense mutation has not been previously reported. Our study revealed that this mutation leads to steric hindrance between residues, causing significant changes in the energy and structure of the FVII protein, ultimately affecting its function. These changes disrupt the normal function of the FVII protein, accelerating the development of inherited FVII deficiency. Moreover, the mRNA expression of the F7 gene and the protein expression of the FVII antigen (FVII: Ag) were significantly lower in the proband, as well as in the proband's parents, compared to the healthy control (P<0.05). Our findings not only elucidate the genetic underpinning of FVII deficiency in the family studied but also contribute a new mutation to the known disease spectrum, potentially assisting in future diagnostic and therapeutic approaches.
Subject(s)
Asian People , Factor VII Deficiency , Factor VII , Heterozygote , Pedigree , Humans , Factor VII Deficiency/genetics , Factor VII/genetics , Factor VII/metabolism , Male , Female , Asian People/genetics , Adult , Mutation, Missense , Mutation , China , East Asian PeopleABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is considered a risk factor for cardiovascular and cerebrovascular disease owing to its close association with coagulant disturbances. However, the precise biological functions and mechanisms that connect coagulation factors to NAFLD pathology remain inadequately understood. Herein, with unbiased bioinformatics analyses followed by functional testing, we demonstrate that hepatic expression of coagulation factor VII (FVII) decreases in patients and mice with NAFLD/nonalcoholic steatohepatitis (NASH). By using adenovirus-mediated F7-knockdown and hepatocyte-specific F7-knockout mouse models, our mechanistic investigations unveil a noncoagulant function of hepatic FVII in mitigating lipid accumulation and lipotoxicity. This protective effect is achieved through the suppression of fatty acid uptake, orchestrated via the AKT-CD36 pathway. Interestingly, intracellular FVII directly interacts with AKT and PP2A, thereby promoting their association and triggering the dephosphorylation of AKT. Therapeutic intervention through adenovirus-mediated liver-specific overexpression of F7 results in noteworthy improvements in liver steatosis, inflammation, injury, and fibrosis in severely afflicted NAFLD mice. In conclusion, our findings highlight coagulation factor FVII as a critical regulator of hepatic steatosis and a potential target for the treatment of NAFLD and NASH.
Subject(s)
Factor VII , Non-alcoholic Fatty Liver Disease , Animals , Humans , Mice , Factor VII/genetics , Factor VII/metabolism , Fatty Acids/metabolism , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
The diagnostic and therapeutic approach for an unusual clinical situation is presented. Twenty-three-year-old female patient is evaluated for hematuria and metrorrhagia. She reported irregular follow-up with hematology because of bleeding in childhood. She has also been receiving factor VII for 2âyears, denying hospitalizations because of bleeding. Laboratory reported hb: 5.2âg/dl; platelets: 234â000/mm 3 ; PT: 100âs; PTT: 112âs, fibrinogen: 90âmg/dl without other alterations. Abdominal ultrasound reported uterine myoma, urinalysis was pathological. The gynecology indicated oral progesterone. She started antibiotic therapy, transfusion of red-blood cells, plasma, and cryoprecipitates and subsequently reported: factor VII: 2%, IX: 1% and VIII: 70%. She received factor VII-recombinant (rFVII), achieving resolution of bleeding. She was prescribed prophylactic rFVII and hematology monitoring. Readmission due to acute abdomen with Hb 5âg/dl, prolonged prothrombin time (PT)/partial thromboplastin time (PTT) and abdominal tomography reported hemoperitoneum. She received rFVII and required laparotomy and left oophorectomy. Then readmission to metrorrhagia, hb6âg/dl, prolonged PT/PTT and factor VII-IX of two coagulation factors were reported, without reports found in the literature consulted.
Subject(s)
Factor IX , Humans , Female , Factor IX/therapeutic use , Factor VII Deficiency/complications , Factor VII Deficiency/drug therapy , Young Adult , Recombinant Proteins/therapeutic use , Adult , Hematuria/etiology , Factor VII/therapeutic useABSTRACT
Age is a significant risk factor for ischemic stroke. However, the influence of aging on coagulation parameters in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) remains unclear. A total of 775 samples were collected from 224 NVAF patients receiving apixaban, edoxaban or rivaroxaban. The samples were categorized into three age groups: (i) ≤ 64 years, (ii) 65-74 years, and (iii) ≥ 75 years (apixaban: N = 48, 108, 119; edoxaban: N = 63, 68, 126; rivaroxaban: N = 115, 90, 38, respectively). Coagulation parameters including fibrinogen (Fbg), factor II, factor V, factor VII, factor X, and D-dimer, were compared between the three age groups for each drug. The slopes in the correlation between drug concentrations and modified diluted prothrombin time (mdPT) were also assessed. Fbg and factor V increased with age, while factor II and factor X decreased. Factor VII and D-dimer showed no significant differences across age categories. The slope in response to drug concentrations was similar between the age groups. In NVAF patients treated with apixaban, edoxaban and rivaroxaban, some coagulation parameters exhibited age-related variation. However, the response of mdPT to drug concentration was consistent across age categories.
Subject(s)
Atrial Fibrillation , Pyridines , Stroke , Thiazoles , Humans , Middle Aged , Rivaroxaban/adverse effects , Warfarin , Anticoagulants , Hemorrhage/drug therapy , Stroke/etiology , Stroke/prevention & control , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/chemically induced , Dabigatran/adverse effects , Factor X/therapeutic use , Factor VII/therapeutic use , Prothrombin , Factor V , Pyridones/therapeutic use , Administration, OralABSTRACT
RATIONALE: Congenital factor VII deficiency is the most common among rare bleeding disorders, characterized by spontaneous or traumatic bleeding. The clinical manifestation is heterogeneous, ranging from asymptomatic phenotype to life-threatening hemorrhages. Intracranial hemorrhage is a common complication of brain tumor neurosurgery, which significantly challenges the perioperative management of patients with hemostatic defects. PATIENT CONCERNS: This report presented a 55-year-old man with congenital factor VII deficiency, who had no history of hemorrhage or family history. He underwent a craniotomy for the treatment of papillary craniopharyngioma. DIAGNOSES: The patient was diagnosed as papillary craniopharyngioma, factor VII deficiency, and atrial fibrillation. INTERVENTIONS: To prevent bleeding, a total of 8 doses of recombinant activated factor VII and 1 dose of fresh frozen plasma were administered as the perioperative replacement therapy. This scheme was guided by a pharmacodynamic evaluation, laboratory tests, and imaging examinations. OUTCOMES: No excessive surgical bleeding was observed during the 22-day treatment. The patient was found to have compound heterozygous mutations, Ala304Thr (c.910G > A) and IVS5-2A > G (c.572-2A > G), in the F7 gene. LESSONS: This is the first reported case in which surgical hemorrhage secondary to brain tumor resection was successfully controlled in the presence of congenital factor VII deficiency. Perioperative coagulation state, hemostasis, and thrombosis events should be closely observed, and the interval and dosage of recombinant factor VIIa should be adjusted accordingly.
Subject(s)
Brain Neoplasms , Craniopharyngioma , Factor VII Deficiency , Neurosurgery , Pituitary Neoplasms , Male , Humans , Middle Aged , Factor VIIa/therapeutic use , Factor VII Deficiency/diagnosis , Craniopharyngioma/complications , Recombinant Proteins/therapeutic use , Blood Loss, Surgical/prevention & control , Brain Neoplasms/drug therapy , Pituitary Neoplasms/complications , Plasma , Factor VII/genetics , Factor VII/therapeutic useABSTRACT
INTRODUCTION: Acquired factor VII (FVII) deficiency is a rare condition with various causes, including acquired inhibitors to FVII, liver disease, and malignancies. Myxoid pleomorphic liposarcoma is a rare and aggressive form of soft tissue sarcoma that can cause a range of clinical manifestations, including bleeding and clotting disorders. PATIENT CONCERNS AND DIAGNOSIS: We present a case report of a 21-year-old man with severe acquired FVII deficiency due to mediastinal myxoid pleomorphic liposarcoma. The patient presented with elevated International normalized ratio (INR) and a severe reduction in FVII coagulant activity, unresponsive to conventional therapy. While an acquired inhibitor to FVII was initially suspected, negative results from laboratory testing, including protein G sepharose adsorption and a Bethesda assay using Immunoglobulin G purified from patient plasma, made the diagnosis of an acquired inhibitor to FVII uncertain. INTERVENTIONS AND OUTCOME: The patient underwent surgical resection of the tumor, supported by recombinant FVII infusion, leading to the normalization of coagulation parameters. However, a relapse of the disease was detected 6 months later when he was noted to have a decline in FVII levels. CONCLUSION: This case highlights the importance of considering rare causes of bleeding and clotting disorders, particularly in unresponsive or atypical presentations. It also underscores the need for close monitoring and follow-up in patients with acquired FVII deficiency, even after successful treatment.
Subject(s)
Factor VII Deficiency , Liposarcoma , Male , Humans , Young Adult , Adult , Factor VII Deficiency/complications , Factor VII Deficiency/diagnosis , Neoplasm Recurrence, Local/drug therapy , Factor VII/metabolism , Hemorrhage/etiology , Blood Coagulation , Liposarcoma/complicationsABSTRACT
Introducción: Los problemas posturales se inician, en la mayoría de los casos, en la infancia, por lo tanto en período de crecimiento una actitud postural alterada compromete el equilibrio cefálico y la posición de la mandíbula pudiendo originar malocluciones. Objetivo: Analizar si existe relación entre el ángulo cráneo-cervical y el patrón esqueletal en una población infantil. Material y métodos: Se evaluaron 70 pacientes con telerradiografía de cráneo de perfil con exámenes cefalométrico de Ricketts con patrón esqueletal de clase I, II y III (Campo II relación cráneo-mandibular, factor 7 convexidad) y el cefalograma de Rocabado, utilizando el ángulo cráneo-vertebral. Resultado: Tanto el sexo como el patrón esqueletal son significativos, su interacción no lo es. A su vez, la edad no resulta significativa. Conclusión: En el presente estudio se encontró que existe relación significativa entre el ángulo cráneo-cervical y el patrón esqueletal (AU)
Introduction: Postural problems begin in most cases, in childhood, therefore during growth an altered postural attitude compromises the cephalic balance and jaw position causing posible malocclucion. Objective: It is to present the correlation between the skull and cervical angle skeletal pattern in a child population. Material and methods: 70 patients were evaluated with teleradiography cephalometric profile tests Ricketts skeletal pattern with class I, II and III (Field II craniomandibular relationship, Factor 7 convexity) and cephalogram Rocabado, using the craniovertebral angle. Result: Both sex and skeletal pattern are significant and their interaction is not. In turn, age is not significant. Conclusion: In the present study it was found that there is a statistically significant relationship between the cranial-cervical angle, and the skeletal pattern (AU)
Subject(s)
Humans , Male , Female , Child , Skull/diagnostic imaging , Cervical Vertebrae/diagnostic imaging , Cephalometry/methods , Malocclusion/diagnostic imaging , Argentina , Posture/physiology , Schools, Dental , Factor VII , Sex Factors , Analysis of Variance , Maxillofacial DevelopmentABSTRACT
Hemofilia adquirida A (HAA) é uma doença rara ? incidênciade 1/1.000.000 ao ano -, com maior prevalência em pessoas de65 a 85 anos. A doença caracteriza-se pela presença de autoanticorposcontra fator VIII (FVIII), o que induz a inibição daligação entre este com fator de Von Willebrand e consequenteinativação de sua função anticoagulante. O objetivo deste trabalhofoi apresentar um caso de Hemofilia adquirida A e destacar anecessidade do médico generalista para o reconhecimento destadoença, visto que sua alta taxa de mortalidade - aproximadamentemais de 20% - a torna um importante diagnóstico diferencialde coagulopatias graves. Paciente do sexo masculino, 59anos, com quadro de dor no ombro esquerdo e evolução parahematomas em diversas partes do corpo. Confirmado o diagnósticode hemofilia adquirida A, iniciou-se o tratamento suportivoe de supressão de inibidor de fator VIII, entretanto, houve novossangramentos. Após terapêutica com ciclofosfamida, foi obtidaa supressão das recorrências dos casos hemorrágicos. Devido aposterior desenvolvimento de anemia, o quimioterápico foi suspenso.Um mês após a retirada do fármaco, o paciente segue semreincidência do quadro. O diagnóstico de hemofilia adquirida Aé evidente caso haja o conhecimento prévio dos achados semiológicose sua rotina de investigação laboratorial, mas frequentementeé atrasado devido à falta de familiaridade com a doençapelos médicos generalistas, fator que interfere diretamente nocurso da Hemofilia adquirida A, pois o diagnóstico precoce éum fator determinante para a redução da taxa de mortalidade.(AU)
Acquired hemophilia A (AHA) is a rare disease ? incidence of1/1.000.000 per year - with a higher prevalence in the elderly.The condition is characterized by the presence of autoantibodiesagainst factor VIII, which induces inhibition of its binding tovon Willebrand factor and consequent inactivation of theiranticoagulant function. The objective of this paper was topresent a case of Acquired hemophilia A and emphasize theneed of primary care physicians to recognize this disease, animportant differential diagnosis of severe coagulopathy, withhigh mortality rate. A fifty-nine years old male patient, withleft shoulder pain and development of hematomas in severalareas of the body. The diagnosis of Acquired hemophilia Awas confirmed and supportive treatment and suppression offactor VIII inhibitor was initiated. However, there was furtherbleeding. After therapy with cyclophosphamide, suppressionof recurrent bleeding cases was obtained. Due to furtherdevelopment of anemia, chemotherapy was discontinued.One month after withdrawal of treatment the patient remainswithout recurrence. The diagnosis of Acquired hemophilia Acan be easier done if there is prior knowledge of the clinicalfindings and interpretation of laboratory investigation. Delayeddiagnosis due to lack of familiarity with the disease by generaldoctors directly interferes in the course of Acquired hemophiliaA, because the early diagnosis is a key factor in reducing themortality rate.(AU)
Subject(s)
Humans , Male , Middle Aged , Factor VII/immunology , Hemophilia A/diagnosis , Prednisone/adverse effects , Cyclophosphamide/adverse effects , Early DiagnosisABSTRACT
Dos polimorfismos pueden tener un importante papel protector contra el infarto de miocardio, debido a que se asocian a una notable disminución de los niveles plasmáticos del factor VII y de la propensión a la trombosis. Objetivo: 1-. Determinar la presencia del polimorfismo Val34leu del Factor XIII en pacientes con infarto del miocardio que ingresan a la unidad de cuidados coronarios (UCC) del HMPC y reciben terapia trombolítica; 2-. Contrastar el efecto de la terapia trombolítica en pacientes con presencia de la mutación y aquellos que no la presentan. Métodos: Se realizó un estudio de campo, descriptivo y correlacional, desde mayo a septiembre del 2007, en la unidad de cuidados coronarios del HMPC-Caracas. La población fue seleccionada mediante criterios de AHA: SCA con elevación del ST, susceptibles a recibir terapia trombolítica. La muestra definitiva, quedo conformada por 30 pacientes. La eficacia de la fibrinólisis fue evaluada por criterios clínicos, electro cardiográfico y enzimático. Una disminución del ST mayor de 50 % a los 90 min y una elevación temprana de las enzimas cardiacas antes de las 12 h fueron considerados criterios de reperfusión. El ADN genómico fue evaluado mediante reacción en cadena de polimerasa. Resultados: El polimorfismo se presento en 39 % de los pacientes estudiados. Se demostró la asociación entre polimorfismo y niveles de fibrinógeno. Conclusiones: Los valores de fibrinógeno estaban disminuidos en la población con polimorfismo en comparación con la que no lo presentaba. La respuesta terapéutica a la terapia trombolítica se relaciono con el fibrinógeno(AU)
Two polymorphisms may have an important protective role against myocardial infarction, because it is associated with a significant decrease in plasma levels of factor VII and the propensity to thrombosis. Objective: 1 -. To determine the presence of Factor XIII Val34Leu polymorphism in patients with myocardial infarction admitted to coronary care unit (CCU) of the HMPC and receives thrombolytic therapy, 2 -. To compare the effect of thrombolytic therapy in patients with presence of the mutation and those without. Methods: We conducted a field study, descriptive, correlation, from May to September 2007 in the coronary care unit of HMPC-Caracas. The population was selected by AHA criteria: ST elevation ACS, likely to receive thrombolytic therapy. The final sample was composed of 30 patients. The effectiveness of fibrinolysis was assessed by clinical, electro cardiograph and enzyme. ST A decrease greater than 50% at 90 min and an early elevation of cardiac enzymes before 12 h reperfusion criteria were considered. DNA was assessed by polymerase chain reaction. Results: The polymorphism was present in 39% of the patients studied. Demonstrated the association between polymorphism and fibrinogen levels. Conclusions: Fibrinogen levels were decreased in the population with polymorphism in comparison with which it had not. The therapeutic response to thrombolytic therapy was associated with fibrinogen(AU)
Subject(s)
Humans , Male , Female , Polymorphism, Genetic , Coronary Thrombosis , Thrombolytic Therapy , Myocardial Infarction , Factor VII , Coronary Disease , Factor XIIIaABSTRACT
La eficacia del tratamiento con factor VII activado recombinante (FVIIar) durante episodios hemorrágicos en pacientes hemofílicos con inhibidores y el conocimiento de su mecanismo de acción, determiná que en los últimos años se ampliara rápidamente su uso en pacientes con hemorragia de diversas causas no controladas con la terapéutica habitual; entre otras, defectos congénitos de la coagulación, trastornos plaquetarios, hepatopatías, cirugía, hemorragia intracraneal, sangramientos digestivos. Aunque un grupo importante de estas comunicaciones se han realizado en forma de casos reportados y serie de casos, se considera que los resultados obtenidos son importantes y que la administración de FVIIar es una alternativa en pacientes con hemorragia grave no controlada. A pesar de su potente acción procoagulante, el riesgo de complicaciones tromboembólicas es bajo y esté relacionado en un grupo importante de pacientes con la presencia de otros factores protrombóticos. En la actualidad se considera que el FVIIar esta indicado en aquellos pacientes con hemorragia masiva que no responden a la terapia con componentes sanguíneos ni a medidas quirúrgicas apropiadas
Effectiveness of the treatment with recombinant activated factor VII (raVII) during the hemorrhagic episodes in hemophilic patients using inhibitions and the knowledge of its action mechanism determined that in pas years its use will be expanded in patients with hemorrhage from non-controlled diverse causes using the usual therapeutics among other, congenital coagulation defects, platelet disorders, liver diseases, surgery, intracranial hemorrhage, digestive bleedings. Although a significant group of these communications have been carried out in reported cases and in cases series, it is considered that the results obtained are important and that the administration of raVII is an alternative in patients presenting with non-controlled severe hemorrhage. Despite its potent pro-coagulant action, thromboembolism complications risk is low and it is related to a significant group of patients with other prothrombotic factors. Nowadays, it is considered that raVII is prescribed in those patients with massive hemorrhage without response either to therapy using blood components or appropriate surgical measures
Subject(s)
Humans , Factor VII/therapeutic use , Hemophilia A/complications , Hemorrhagic Disorders/drug therapy , Case ReportsABSTRACT
Antecedentes. En el enfermo grave, la hemorragia crítica aguda refractaria al manejo convencional es una complicación frecuente de etiología multifactorial con alta morbilidad y mortalidad. El factor VII recombinante activado (FVIIra) es una nueva alternativa terapéutica en estos casos. Objetivo. Presentar el análisis descriptivo en pacientes no hemofílicos con hemorragia grave tratados con FVIIra. Material y métodos. Diez pacientes no hemofílicos con hemorragia grave, cinco hombres y cinco mujeres, edad entre 18 y 74 años, tratados con FVIIra. Se aplicó una prueba de t para el análisis estadístico. Se consideró una p < 0.001 como significativa. Resultados. Después de la administración del FVIIra se controló la hemorragia y disminuyó el uso de hemoderivados en los diez pacientes tratados (p < 0.001). Los tiempos de coagulación, concentraciones de fibrinógeno, cuenta plaquetaria y parámetros de perfusión tisular mejoraron significativamente después de la aplicación del FVIIra (p < 0.001). Conclusiones. El FVIIra es una alternativa terapéutica útil en enfermos graves que cursan con hemorragia crítica aguda no controlada con el manejo convencional.
BACKGROUND: Severe hemorrhage is a frequent complication with multiple etiologies and high morbi-mortality observed among critically ill patients. Recombinant Factor VIla (rFVlla) constitutes a new therapeutic alternative. OBJECTIVE: Analyze the evolution in a non-hemophiliac patient group with severe hemorrhage treated with rFVlla. MATERIAL AND METHODS: Ten non-hemophiliac patients with severe hemorrhage, five men and five women between 18 and 74 years, were included and treated with rFVIIa. We used a t test for statistic analyses. Significance was set at p < 0.001. RESULTS: Among patients treated with rFVlla, hemorrhage was controlled and the use of blood products was significantly diminished (p < 0.001). Coagulation tests, fibrinogen levels, platelet count and perfusion parameters increased significantly (p < 0.001). CONCLUSIONS: rFVIIa is a therapeutic alternative for the treatment of severe hemorrhage not controlled by conventional management.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Factor VII/therapeutic use , Hemorrhage/drug therapy , Acute Disease , Blood Coagulation Tests , Blood Component Transfusion , Critical Illness , Factor VIIa , Intensive Care Units , Recombinant Proteins/therapeutic use , Treatment OutcomeABSTRACT
Background: Neonates on exclusive breast feeding that do not receive vitamin K at birth are at higher risk hemorrhagic disease of the newborn. Aim: To compare the effect of oral or intramuscular administration of vitamin K1 (VK1), on clotting factors II, VII, IX, X and PIVKA II, in children until the 60 days of age with exclusive breast feeding or mixed feeding. Patients and methods: Forty healthy full term infants, distributed in two groups, A: 20 with mixed feeding (formula-feeding and breast-feeding) and B: 20 with exclusive breast feeding, were studied. Nine infants of each group received 1 mg of VK1 intramuscularly and eleven 2 mg VK orally. 5 ml of cord blood was collected initially from each infant. Venous blood samples were taken on 15, 30 and 60 days of age. Results: All factors increased in a progressive form reaching levels over 50 per cent at 60 days of age, in both groups. PIVKA II decreased significantly during the study period (p <0.01). Factor II increased more in children with mixed feeding that received intramuscular vitamin K, than in the rest of study groups. No other differences between groups were observed. No infant had an abnormal bleeding during the study period. Conclusions: Oral administration of vitamin K is as effective as the intramuscular route in the prevention of the hemorrhagic disease of the newborn (Rev MÄd Chile 2001; 129: 1121-9)
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Vitamin K , Breast Feeding , Factor IX , Factor VII , Factor X , Prothrombin , Injections, Intramuscular , Administration, Oral , Nutritional SupportABSTRACT
Fueron evaluados 85 sujetos de Ocumare de la Costa-Aragua, edades entre 20 y 56 años. Se clasificaron en normotensos (<120 y <80 mmHg, n=40) e hipertensos (n=45). Se determinó factor VII antigénico (FVIIag) por ELISA (V.R=70-130 por ciento). Se obtuvo niveles de FVIIag de 55,42 por ciento ñ 12,45 vs. 57,86 por ciento ñ 13,50; para normotensos e hipertensos respectivamente. El FVIIag fue mayor en hipertensos masculinos (64,41 por ciento ñ 10,74; p<0,05). Se incrementó con la edad en hipertensos (63,16 por ciento ñ 11,24; p<0,01). La ingesta de alcohol disminuyó ligeramente los valores de FVIIag en normotensos e hipertensos. Los hipertensos sedentarios presentaron valores significativamente más elevados (73,66 por ciento ñ 6,6; p<0,05). Se concluye que niveles elevados de FVIIag se relacionan con hipertensión arterial y estilos de vida