RESUMO
Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9, or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.
Assuntos
Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Biologia Computacional/métodos , Fator IX/genética , Testes Genéticos/métodos , Hemofilia A/genética , Fator de von Willebrand/genética , Transtornos Herdados da Coagulação Sanguínea/genética , Colômbia , Biologia Computacional/economia , Biologia Computacional/normas , Custos e Análise de Custo , Fator IX/química , Testes Genéticos/economia , Testes Genéticos/normas , Hemofilia A/diagnóstico , Humanos , Domínios Proteicos , Sensibilidade e Especificidade , Fator de von Willebrand/químicaRESUMO
INTRODUCTION: Heavy Menstrual Bleeding (EMB) is a frequent problem in adolescence. The prevalence of inherited bleeding disorders (IBD) as a cause of EMB is not well established and the involvement of fibri nolytic pathway defects has been poorly explored. OBJECTIVE: To determine the prevalence of IBD and fibrinolysis defects in adolescents with EMBs. PATIENTS AND METHOD: 93 adolescents (11 to 18 years old) were included. Personal and family history of bleeding were obtained through a standard ized questionnaire. The following lab tests were performed: prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor quantification, and platelet count and function. Those patients who were not diagnosed with IBD were further evaluated with clot lysis time assay. RESULTS: 41 patients (44%) were diagnosed as IBD (Von Willebrand disease n = 28, platelet func tion defects n=8, mild hemophilia n = 5. Decreased clot lysis time was found in 31 patients. 54% of patients diagnosed with IBD had EMB as the first hemorrhagic manifestation. CONCLUSION: These results support the need to evaluate the coagulation process, including the fibrinolytic pathway in the study of adolescents with EMB.
Assuntos
Transtornos Herdados da Coagulação Sanguínea/complicações , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Fibrinólise , Menorragia/etiologia , Adolescente , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos Herdados da Coagulação Sanguínea/epidemiologia , Transtornos Herdados da Coagulação Sanguínea/fisiopatologia , Testes de Coagulação Sanguínea , Criança , Estudos Transversais , Feminino , Humanos , PrevalênciaRESUMO
Resumen: Introducción: El Sangrado Menstrual Excesivo (SME) es un problema frecuente en la adolescencia. La prevalencia de trastornos hereditarios de la coagulación (THC) como causa del SME no está bien establecida y la participación de defectos de la vía fibrinolítica ha sido poco explorada. Objetivo: Determinar la prevalencia de THC y defectos de la fibrinólisis en adolescentes con SME. Pacientes y Método: Se incluyeron 93 adolescentes, edad 11 a 18 años. Los antecedentes personales y familiares de sangra do se obtuvieron con un cuestionario estandarizado. Se controló exámenes: tiempo de protrom- bina (TP), tiempo de tromboplastina parcial activada (TTPa), estudio del factor Von Willebrand, recuento y función plaquetaria. Los pacientes que no fueron diagnosticados como THC, se evaluaron adicionalmente con el tiempo de lisis del coágulo. Resultados: 41 pacientes (44%) fueron diagnos ticados como THC: Enfermedad de Von Willebrand n = 28, defectos de la función plaquetaria n = 8, hemofilia leve n = 5. Se confirmó disminución del tiempo de lisis del coágulo en 31 pacientes. El 54% de pacientes diagnosticado como THC, tuvo SME como la primera manifestación hemorrágica. Conclusión: Estos resultados apoyan la necesidad de evaluación de la coagulación, incluyendo la vía fibrinolítica, en el estudio de adolescentes con SME.
Abstract: Introduction: Heavy Menstrual Bleeding (EMB) is a frequent problem in adolescence. The prevalence of inherited bleeding disorders (IBD) as a cause of EMB is not well established and the involvement of fibri nolytic pathway defects has been poorly explored. Objective: To determine the prevalence of IBD and fibrinolysis defects in adolescents with EMBs. Patients and Method: 93 adolescents (11 to 18 years old) were included. Personal and family history of bleeding were obtained through a standard ized questionnaire. The following lab tests were performed: prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor quantification, and platelet count and function. Those patients who were not diagnosed with IBD were further evaluated with clot lysis time assay. Results: 41 patients (44%) were diagnosed as IBD (Von Willebrand disease n = 28, platelet func tion defects n=8, mild hemophilia n = 5. Decreased clot lysis time was found in 31 patients. 54% of patients diagnosed with IBD had EMB as the first hemorrhagic manifestation. Conclusion: These results support the need to evaluate the coagulation process, including the fibrinolytic pathway in the study of adolescents with EMB.
Assuntos
Humanos , Feminino , Criança , Adolescente , Transtornos Herdados da Coagulação Sanguínea/complicações , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Fibrinólise , Menorragia/etiologia , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea , Prevalência , Estudos Transversais , Transtornos Herdados da Coagulação Sanguínea/fisiopatologia , Transtornos Herdados da Coagulação Sanguínea/epidemiologiaRESUMO
The best-known inherited mild bleeding disorders (MBDs), i.e. type 1 von Willebrand disease (VWD), platelet function disorders (PFDs), and mild to moderate clotting factor deficiencies, are characterized clinically by mucocutaneous bleeding, and, although they are highly prevalent, still pose difficult diagnostic problems. These include establishing the pathological nature of bleeding, and the uncertainties surrounding the clinical relevance of laboratory results. Furthermore, the high frequency of bleeding symptoms in the normal population and the subjective appraisal of symptoms by patients or parents makes elucidating the pathological nature of bleeding difficult. Standardized bleeding assessment tools and semiquantitative bleeding scores (BSs) help to discriminate normal from abnormal bleeding. However, as most MBDs have similar bleeding patterns, for example, bleeding sites, frequency, and severity, BSs are of little help for diagnosing specific diseases. Global tests of primary hemostasis (bleeding time; PFA-100/200) lack sensitivity and, like BSs, are not disease-specific. Problems with the diagnosis of type 1 VWD and PFD include assay standardization, uncertain definition of von Willebrand factor cut-off levels, and the lack of universal diagnostic criteria for PFD. Regarding clotting factor deficiencies, the bleeding thresholds of some coagulation factors, such as factor VII and FXI, are highly variable, and may lead to misinterpretation of the clinical relevance of mild to moderate deficiencies. Remarkably, a large proportion of MBDs remain undiagnosed even after comprehensive and repeated laboratory testing. These are tentatively considered to represent bleeding of undefined cause, with clinical features indistinguishable from those of classical MBD; the pathogenesis of this is probably multifactorial, and unveiling these mechanisms should constitute a fertile source of translational research.
Assuntos
Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea , Coagulação Sanguínea/genética , Transtornos Plaquetários/diagnóstico , Testes de Função Plaquetária , Animais , Transtornos Herdados da Coagulação Sanguínea/sangue , Transtornos Herdados da Coagulação Sanguínea/genética , Transtornos Plaquetários/sangue , Transtornos Plaquetários/genética , Diagnóstico Diferencial , Predisposição Genética para Doença , Humanos , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Doença de von Willebrand Tipo 1/sangue , Doença de von Willebrand Tipo 1/diagnóstico , Doença de von Willebrand Tipo 1/genéticaRESUMO
BACKGROUND: Superficial vein thrombosis (SVT) is a common venous condition. Recent studies have shown that SVT is associated with high frequency of thromboembolic complications: from 22-37% for deep venous thrombosis and up to 33% for pulmonary embolism. Our goal was to assess the prevalence of major hereditary and acquired thrombophilic factors in patients with SVT. METHODS: Sixty-six patients presenting with primary SVT underwent evaluation for thrombophilia: molecular testing for the factor V Leiden and factor II G20210 A (prothrombin) mutations, protein C, protein S, antithrombin deficiency, presence of lupus anticoagulant, as well as anticardiolipin antibody titers. Patients aged less than 18 years, with confirmed deep vein thrombosis, and pregnant women were excluded. RESULTS: 95.5% were Caucasian, and 62.1% were female gender. Age ranged from 21-88 years. Molecular testing showed that 34.2% of patients were heterozygous for factor V Leiden, 23.6% were heterozygous for the factor II mutation, 7.8% had antithrombin deficiency, 2.6% had protein S deficiency, and 2.1% had protein C deficiency. CONCLUSIONS: Our study showed that hereditary and acquired thrombophilias are higher than previously expected and reported.
Assuntos
Transtornos Herdados da Coagulação Sanguínea/epidemiologia , Coagulação Sanguínea , Extremidade Inferior/irrigação sanguínea , Trombofilia/epidemiologia , Trombose Venosa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticardiolipina/sangue , Coagulação Sanguínea/genética , Transtornos Herdados da Coagulação Sanguínea/sangue , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Transtornos Herdados da Coagulação Sanguínea/genética , Fatores de Coagulação Sanguínea/genética , Brasil/epidemiologia , Estudos Transversais , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Inibidor de Coagulação do Lúpus/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Prevalência , Fatores de Risco , Trombofilia/sangue , Trombofilia/diagnóstico , Trombofilia/genética , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/genética , Adulto JovemRESUMO
Introducción: la hemostasia es el conjunto de sistemas que actúan coordinadamente para mantener la integridad de los vasos sanguíneos y la fluidez de la sangre; la alteración puede desencadenar trastornos trombóticos o hemorrágicos, dependiendo de la naturaleza de la falla. Objetivos: describir las coagulopatías hemorrágicas que se registraron en el departamento de laboratorio del Hospital Nacional de Itauguá, desde julio 2014 hasta diciembre 2015, obtener frecuencia y datos demográficos, edad, sexo, procedencia y clasificar las coagulopatías según deficiencias de factores de la coagulación, vía extrínseca, vía intrínseca y vía común final; sospecha de inhibidores adquiridos y enfermedad de von Willebrand. Material y Métodos: diseño observacional, descriptivo, retrospectivo de corte trasverso; incluyéndose pacientes de ambos sexos, todas las edades, derivados de médicos hematólogos. Resultados: se registraron 77 pacientes con coagulopatías hemorrágicas en el Laboratorio, 43 fueron del sexo masculino, de 1 a 75 años, mediana 18 años; 31% (24/77) con deficiencias del factor VII, todos leves, edades 7 a 75 años. En la vía intrínseca, la deficiencia del factor VIII o Hemofilia A, fue la más observada 29%(22/77), mayoría severas (13/22), mientras que déficit de factor IX, Hemofilia B, en 4 pacientes 5%(4/77). 85% Hemofilia A y 15% Hemofilia B, edades 1 y 64 años, mediana 13,5 años, todos del sexo masculino; no se registraron deficiencias de FXI y FXII en el periodo de estudio. De la vía común final, se encontraron 3 pacientes con hipofibrinogenemia, 1 con probable disfibrinogenemia, 1 con déficit de Factor II, 2 de Factor V y 2 de Factor X, 2 adultas, y el resto pediátricos; estas deficiencias son muy poco frecuentes, Factor I, V y X de 1/1.000.000 y FII 1/2.000.000 personas. Quince pacientes con sospecha de inhibidores, dos de ellas con inhibidor específico anti-FVIII, y probables inhibidores de interferencia. Se confirmó el primer déficit de factor Von Willebrand, en una mujer de 47 años. Conclusiones: entre las coagulopatías hemorrágicas de mayor frecuencia, se encuentran las Hemofilias A y B, seguida de deficiencias del factor VII y probables inhibidores de interferencia, los dos casos de inhibidores específicos anti Factor VIII fueron en pacientes con Hemofilia A severa. Fue relevante también el hallazgo de deficiencias de la vía común de la coagulación, a pesar de ser poco frecuentes. Algunos pacientes fueron diagnosticados en edad adulta, reflejando lo tardío que se llega al diagnóstico en el país.
Introduction: hemostasis is the set of systems that work in concert to maintain the integrity of blood vessels and blood flow; alteration can trigger thrombotic disorders or bleeding, depending on the nature of the fault Objective: describe hemorrhagic coagulopathy registered in the Medical Laboratory Department diagnosis at the National Hospital of Itauguá, from July 2014 to December 2015, obtain frequency and demographics, age, sex, origin and classify coagulopathy in to deficiencies of coagulation factors of the extrinsic pathway, intrinsic pathway, and common pathway; suspicion acquired inhibitors and von Willebrand's disease. Material and Methods: the design was an observational, descriptive, retrospective cross sectional study; being including patients of both sexes, all ages, referred by hematologists. Results: 77 patients with hemorrhagic coagulopathies, were female 43 male and 34 female, from 1 to 75 years, median age of 18 years; 31% (24/77) with factor VII deficiency, all mild, ages 7 to 75, 1 / 500,000 appears. In the intrinsic pathway, the factor VIII deficiency or hemophilia A, was the most observed 29% (22/77) severe majority (13/22), while Factor IX deficit, Hemophilia B, in 5% of patients (4/77). 85% Hemophilia A, and 15% Hemophilia B, ages 1 to 64 years, median age of 13.5 years, all male; no FXI and FXII deficiencies were recorded in the study period.Of the final common pathway, 3 patients with hipofibrinogenemia were found, 1 probable dysfibrinogenaemia, 1 deficiency of FII, 2 FV and FX 2, 2 were adult and the rest were pediatric; these deficiencies are rare, FI, V and X of 1 / 1,000,000 and FII 1 / 2,000,000 people. Fifteen patients with suspected inhibitors adquired, two of them with anti-FVIII specific inhibitor, and probable interference inhibitors. The first von Willebrand, factor deficiency was confirmed in a woman of 47 years. Conclusions: among the most frequent hemorrhagic coagulation disorders, we found hemophilia A and B, followed by deficiencies of factor VII and probable interference inhibitors both cases of specific inhibitors of factor VII were found in patients with severe Hemophilia A. Some patients were diagnosed in adulthood
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Transtornos de Proteínas de Coagulação/diagnóstico , Doenças de von Willebrand/diagnóstico , Estudos Transversais , Estudos Retrospectivos , Hemofilia B/diagnóstico , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Deficiência do Fator VII/diagnóstico , Hemofilia A/diagnósticoRESUMO
Se detalla y fundamenta la técnica de extracción atraumática de dientestemporales unirradiculares en pacientes pediátricos con trastornos de lacoagulación utilizando separadores elastoméricos. Se expone el caso deun paciente pediátrico con diagnóstico de defi ciencia de factor X de lacoagulación, quien requirió de la extracción atraumática de los órganosdentarios centrales superiores temporales debido a la gingivorragiapropia de la exfoliación natural.
We describe the technique of atraumatic tooth extraction for single-rooted temporary and permanent teeth in pediatric patients with bleed-ing disorders using elastomeric separators and discuss its benefi ts. We present the case of a pediatric patient diagnosed with coagulation factor X defi ciency who required the atraumatic extraction of his temporary upper central teeth due to gingival bleeding caused by natural exfoliation.