Orthognathic surgery in a patient with von Willebrand disease: case report

Aim: This study aims to report the perioperative management of a patient with von Willebrand disease (vWd) who underwent orthognathic surgery. The report follows the guidelines of the Case Report Guidelines (CARE) and focuses on the steps taken to prevent bleeding during the surgical procedure. Methods: A 39-year-old female patient with skeletal Class III was treated with maxillary advancement and mandibular setback. Despite normal test results for ristocetin cofactor activity, measures were taken to prevent bleeding, including atraumatic surgical techniques, use of antifibrinolytic medication, induced hypotension during anesthesia, and preparation of blood products for transfusion during trans and postoperative periods if needed. In the end, these measures were not required. Results: The patient did not experience any bleeding during the surgical procedure or postoperative period, demonstrating the effectiveness of the measures taken to manage their blood dyscrasia. Two years after the surgery, the patient had satisfactory aesthetic and functional results and no evidence of relapse. Conclusion: Thus, this case report demonstrates that vWd does not prevent largescale oral and maxillofacial surgeries such as orthognathic surgery as long as proper precautions are taken pre-, intraand postoperatively

Diagnóstico de la enfermedad de von Willebrand / Diagnosis of von Willebrand disease

La enfermedad de von Willebrand (EVW) es el trastorno hemorrágico hereditario más común, y se caracteriza por presentar disminución de la capacidad del factor von Willebrand (FVW) de unirse a las plaquetas y al colágeno de la matriz extracelular durante la hemostasia primaria, debido a defectos cuantitativos o cualitativos. La EVW se clasifica en tres fenotipos principales: el 1 y el 3 que son trastornos cuantitativos, y el 2 que se subclasifica en 2A, 2B, 2M y 2N, y refleja los trastornos cualitativos. Para su diagnóstico son necesarios varios pasos: 1) la evaluación del historial de sangrado personal y familiar del paciente, 2) detección inicial de trastornos hemorrágicos, 3) pruebas para la detección de la EVW, 4) pruebas para la tipificación de la EVW, y 5) el análisis molecular. Tanto la subclasificación de la EVW como su diagnóstico continúan planteando desafíos importantes, motivo por el cual se realiza esta revisión, de manera que los profesionales de la salud tengan una guía que los oriente al momento de tener pacientes con algún trastorno hemorrágico que amerite descartar una EVW e implementar un tratamiento adecuado

von Willebrand disease (VWD) is the most common hereditary bleeding disorder, and is characterized by a decreased ability of the von Willebrand factor (VWF) to bind to platelets and extracellular matrix collagen during primary hemostasis, due to quantitative or qualitative defects. VWD is classified into three main phenotypes: 1 and 3, which are quantitative disorders, and 2 (2A, 2B, 2M and 2N) that reflects qualitative disorders. Several steps are necessary for its diagnosis: 1) evaluation of the patient's personal and family bleeding history, 2) initial screening tests for bleeding disorders, 3) tests for the detection of VWD, 4) tests for the classification of VWD, and 5) molecular analysis. Both the subclassification of VWD and its diagnosis continue to represent important challenges, which we aimed to describe in this review, so that health professionals have a guide to assist them when they have patients with a bleeding disorder that requires exclusion of VWD, and implementation of an appropriate treatment.

Antígeno del factor von Willebrand (FVW: Ag) / von Willebrand factor antigen (VWF: Ag)

Utilidad clínica de la prueba El factor von Willebrand (FVW) es una glicoproteína compuesta por multímeros con pesos moleculares que pueden variar desde 500 KDa hasta 20.000 kDa, que se sintetiza en las células endoteliales y en los megacariocitos, y se almacena en los cuerpos de Weibel-Palade y en los gránulos alfa de las plaquetas [1]. El papel del FVW en la hemostasia primaria es mediar la adhesión de las plaquetas a los componentes de la matriz extracelular, a través de los complejos glucoproteicos plaquetarios GPIbα y αIIb3ß; en la hemostasia secundaria, se asocia con el factor VIII para prevenir su degradación y favorecer la generación de trombina para la formación del trombo final

Seguridad de la endoscopia y biopsia esofágica en un paciente con esofagitis eosinofílica y enfermedad de Von Willebrand / Safety of esophageal endoscopy and biopsy in a patient with eosinophilic esophagitis and Von Willebrand disease

La esofagitis eosinofílica (EoE) es una enfermedad causada por una respuesta inmune frente a antígenos alimentarios en contacto con la mucosa esofágica; por su parte, la enfermedad de Von Willebrand (EVW) es el trastorno hemorrágico hereditario más común en los seres humanos. La característica central de todos los tipos de EVW, es la presencia de cantidades reducidas o de formas anormales del factor de Von Willebrand (FVW) en el torrente sanguíneo. Debido a que no se han reportado casos previos de EVW tipo 2A asociada a EoE, se describe este caso clínico con el objetivo principal de dar a conocer el hallazgo casual de estas dos patologías, la seguridad de la evaluación por endoscopia de vías digestivas altas y el pronóstico de posibles complicaciones

Eosinophilic esophagitis (EoE) is a disease caused by an immune response against food antigens in contact with the esophageal mucosa; alternatively, Von Willebrand disease (VWD) is the most common inherited bleeding disorder in humans. The central characteristic of all types of VWD is the presence of reduced amounts or abnormal forms of VWF in the bloodstream. Since no previous cases of VWD type 2A associated to EoE have been reported, this clinical case is described with the main objective to present the coincidental finding of these two pathologies, the safety of the evaluation by upper gastrointestinal endoscopy, and the prognosis of possible complications

Estudio de la relación entre el grupo sanguíneo eritrocitario ABO con los niveles del factor von Willebrand en pacientes diagnosticados con la enfermedad / Study of the relationship between the ABO erythrocyte blood group with the von Willebrand factor levels in patients diagnosed with the disease

Resumen La presencia o ausencia de los antígenos del sistema ABO entre otros factores se han relacionado con los niveles plasmáticos del factor von Willebrand (VWF) debido a su influencia en la proteólisis por la ADAMTS 13; la actividad de este sistema eritrocitario puede incidir en eventos trombóticos o hemorrágicos. El propósito de este estudio fue determinar si los pacientes diagnosticados con la enfermedad de von Willebrand pertenecían al grupo sanguíneo O y si los niveles de VWF y FVIII eran más bajos que los de los grupos no-O. El grupo sanguíneo fue identificado por un método directo en tubo y el VWF y FVIII se midieron mediante ensayos de coagulación. Se analizó un total de 64 pacientes, el 29,4% eran mayores de 40 años, el 100% presentaron valores más bajos del VWF que los grupos no-O, el 64% de los pacientes presentaron una concentración del FVIII de 6-49% inferior al rango normal establecido y el 78,51% fueron tipificados como del grupo sanguíneo O. El análisis estadístico demostró una relación estadísticamente significativa entre los niveles de VWF y el grupo sanguíneo. Se determinó que existe una relación entre el sistema ABO y el VWF-FVIII (p<0,05); sin embargo, esto no significa que sea la única causa de la existencia de un nivel bajo del factor. Estos datos indican la necesidad de mayores estudios en la población de pacientes con la enfermedad y la necesidad de determinar los tipos de von Willebrand y su relación con el grupo sanguíneo.

Abstract The presence or absence of antigens of the ABO system, among other factors, have been related to plasma levels of von Willebrand factor (VWF) due to its influence on proteolysis by ADAMTS 13. The activity of this erythrocyte system may influence on thrombotic or hemorrhagic events. The purpose of this study was to determine if the patients diagnosed with von Willebrand disease belonged to the O blood group and the VWF and FVIII levels were lower than those of the other blood groups. The blood group was identified by direct tube method and the VWF and FVIII were measured by coagulation tests. A total of 64 patients were analised, 29.4% were older than 40, 100% presented lower values of VWF than the non-O groups. A total of 64% of the patients presented a lower concentration of 6-49% in FVIII at the established normal range and 78.51% were typified as blood group O. Statistical analysis showed a statistically significant relationship between VWF levels and blood group. It was determined that there is a relationship between the ABO system and the VWF-FVIII (p<0.05). However, this does not mean that is the only cause of the existence of a low level of these factors. These data indicate the need for further studies in the population of patients with von Willebrand disease in order to determine the von Willebrand types and their relationship with the blood group.

Resumo A presença ou ausência dos antígenos do sistema ABO, entre outros fatores, tem sido relacionada aos níveis plasmáticos do fator de von Willebrand (VWF) devido à sua influência na proteólise pelo ADAMTS 13; a atividade desse sistema eritrocitário pode afetar eventos trombóticos ou hemorrágicos. O objetivo deste estudo foi determinar se os pacientes com diagnóstico de doença de von Willebrand pertenciam ao grupo sanguíneo O e se os níveis de VWF e FVIII eram inferiores aos dos grupos não-0. O grupo sanguíneo foi identificado por um método direto em tubo e o VWF e o FVIII foram medidos por testes de coagulação. Foram analisados 64 pacientes, 29,4% tinham idade superior a 40 anos, 100% apresentaram valores mais baixos do VWF que os grupos não-O e 64% dos pacientes apresentaram concentração de FVIII 6-49% menor à faixa normal estabelecida, e 78,51% foram tipificados como do grupo sanguíneo O. A análise estatística mostrou uma relação estatisticamente significativa entre os níveis de VWF e o grupo sanguíneo. Foi determinado que existe uma relação entre o sistema ABO e o VWF-FVIII (p<0,05), no entanto, isso não significa que seja a única causa da existência de um baixo nível do fator. Esses dados indicam a necessidade de novos estudos na população de pacientes com a doença e a necessidade de determinar os tipos de von Willebrand e sua relação com o grupo sanguíneo.

Desmopressin acetate use in von Willebrand's disease: a survey on current practices in Brazil

ABSTRACT Introduction: von Willebrand's disease (VWD) is the most common inherited bleeding disorder. The 1-desamino-8-d-arginine vasopressin (DDAVP) is the treatment of choice for most responsive patients with VWD. The aim of this study was to evaluate DDAVP use in the management of VWD. Method: We implemented a survey targeting medical doctors involved in the management of VWD in Brazil. Data was collected during a national congress on Hematology in November 2017. Main results: A total of 51/80 (63.8%) questionnaires were collected. Most participants (76.2%) were hematologists who assisted adult patients and approximately 60% worked at hemophilia treatment centers (HTCs). Approximately half of participants who reported treating patients with VWD, assisted on average, less than 5 patients per month, and approximately 60% declared not having used any DDAVP for treating VWD in the previous year. However, most participants (70%) prescribed FVIII-containing VWF concentrate (VWF/FVIII) for 1-10 patients in the previous year. More than 80% of the participants recognized the main indications for DDAVP. Physicians who recognized indication for DDAVP for type 1 VWD more often had prescribed DDAVP in previous year (p = 0.03). Barriers for prescribing DDAVP varied and included unavailability of laboratory facilities and consumables for DDAVP testing and lack of skills on its prescription. Conclusion: The DDAVP is currently underused in Brazil, as opposed to the excessive use of VWF/FVIII in VWD patients. We suggest the adoption of measures targeting educational and auditing programs. Furthermore, availability of laboratory reagents is needed to evaluate response and increment the correct use of DDAVP.

Diagnóstico laboratorial da doença de Von Willebrand: uma revisão de literatura / Laboratory diagnosis of Von Willebrand disease: a literature review

A doença de Von Willebrand (DVW) é o distúrbio hemorrágico mais comum decorrente de disfunção qualitativa ou quantitativa do fator de Von Willebrand (FVW) podendo ser adquirida ou congênita. De acordo com a Federação Mundial de Hemofilia de 2017, do total de 315.423 pessoas portadoras de coagulopatias hereditárias, 76.144 são portadoras da DVW com prevalência no Brasil de 8.531 portadores para um total de 209.288.278 brasileiros. É frequentemente subdiagnosticada por profissionais de saúde devido ao desconhecimento de suas apresentações clínicas, indisponibilidade de testes laboratoriais específicos ou dificuldades técnicas para a realização desses testes. Com base na gravidade e subdiagnóstico da DVW, o objetivo deste estudo foi revisar a literatura existente para descrever a doença e os exames laboratoriais para o diagnóstico das alterações ocasionadas na hemostasia a fim de evidenciar a importância do conhecimento pelos profissionais da saúde e proporcionar melhor acompanhamento dos pacientes. Trata-se de um estudo descritivo de revisão da literatura de artigos completos, monografias, dissertações e teses indexadas nas bases de dados MEDLINE, SCIELO, LILACS, BIREME e Biblioteca Virtual de Saúde, utilizando as palavras-chave: Fator de Von Willebrand, Doença de Von Willebrand e Diagnóstico Laboratorial, no período entre 2000 e 2019, nos idiomas português e inglês. O FVW é essencial durante a coagulação sanguínea por ser responsável pela ativação plaquetária, pela formação do tampão plaquetário e por manter níveis plasmáticos adequados do Fator VIII. O diagnóstico da DVW é de extrema importância, pois ela oferece graves riscos ao indivíduo quando subdiagnosticada. Esse diagnóstico requer conhecimento técnico dos profissionais de saúde para o correto tratamento, pois a variedade de tipos e subtipos que apresenta pode ocasionar falhas no diagnóstico. Sugere-se maiores esclarecimentos aos profissionais de saúde por meio de educação permanente com médicos Hematologistas para um diagnóstico preciso e confiável.

Von Willebrand Disease (VWD) is the most common hemorrhagic disorder related to a qualitative or quantitative dysfunction of the Von Willebrand Factor (VWF); it can be acquired or congenital. According to the World Federation of Hemophilia, out of 315,423 people with hereditary coagulopathies, 76,144 are carriers of the VWD. In Brazil, there is a prevalence of 8,531 carriers out of 209,288,278 Brazilians. It is often underdiagnosed by health professionals due to the lack of knowledge of its clinical presentations, unavailability of specific laboratory tests, or technical difficulties to perform these tests. Based on the severity and underdiagnosis of VWD, this study aimed to review the literature to describe the disease and the changes caused in hemostasis to highlight the importance of providing knowledge to health professionals and a better monitoring of patients. This is a descriptive study carried out through a literature review of complete articles, final papers, dissertations, and theses, indexed on MEDLINE, SCIELO, LILACS, BIREME, and on the Virtual Health Library, using the keywords: Coagulopathy, Von Willebrand Factor, and Von Willebrand Disease, between 2000 to 2019, in Portuguese and English. VWF is essential during blood clotting because it is responsible for the activation of platelet, formation of a platelet plug, and maintenance of adequate plasma levels of Factor VIII. The diagnosis of VWD is essential because it offers grave risks to the individual when underdiagnosed. It requires technical knowledge from health professionals for the correct treatment since its variety of types and subtypes can cause failures in the diagnosis. Further clarification is suggested to health professionals through permanent education with Hematologists for an accurate and reliable diagnosis.

El síndrome de Heyde / Heyde syndrome / Síndrome de Heyde

Desde que Edward Heyde vislumbró en 1958 una misteriosa asociación entre estenosis aórtica y hemorragia digestiva han transcurrido seis décadas y se ha suscitado no poca controversia. En la época en que fue propuesta, el estatus técnico y metodológico de la ciencia médica y una interpretación sesgada de su idea original impidieron obtener un sustento estadístico y fisiopatológico que le otorgara un amplio reconocimiento como entidad clínica individual. Los avances en varias disciplinas permitieron demostrar que su frecuencia de presentación excede el efecto del azar, además de esclarecer con precisión y elegancia sus mecanismos fisiopatológicos. Su consolidación como síndrome nos revela una verdadera encrucijada entre la cardiología, la gastroenterología, la hematología y el laboratorio, especialidades involucradas tanto en su proceso de comprensión como en su manejo práctico en la actualidad. Sin embargo, a pesar de tener una incidencia no desdeñable y adquirir un papel central en la conducción clínica de la estenosis aórtica, esta entidad parece haber pasado de ser resistida a relativamente ignorada. Con el objetivo de contribuir a su visibilidad, la presente revisión ofrece un panorama integral sobre el tema, incluyendo una perspectiva histórica de los principales aportes en pos de su conocimiento y un abordaje en profundidad de sus mecanismos, las claves de su detección clínica y su impacto en el manejo de la estenosis aórtica y otras entidades con fisiopatología afín.

Since Edward Heyde perceived in 1958 a mysterious association between aortic stenosis and gastrointestinal bleeding, six decades have passed and no little controversy has arisen. At the time it was proposed, the technical and methodological status of medical science and a biased interpretation of his original idea prevented obtaining a statistical and pathophysiological support that would grant it wide recognition as and individual clinical entity. Advances in several disciplines allowed to demonstrate that its frequency of presentation exceeds the effect of chance, besides clarifying with precision and elegance its pathophysiological mechanisms. Its consolidation as a syndrome reveals a true crossroads between Cardiology, Gastroenterology, Hematology and Laboratory, specialties involved both in its understanding process and in its practical management today. However, despite having a not negligible incidence and acquiring a central role in the clinical conduction of aortic stenosis, this entity seems to have gone from being resisted to relatively ignored. With the objective of contributing to its visibility, this review offers a comprehensive overview of the subject, covering the main historical contributions to its knowledge and approaching in depth its mechanisms, the keys to its clinical detection and its impact on the management of aortic stenosis and other entities with related pathophysiology.

Desde que Edward Heyde imaginou em 1958 uma misteriosa associação entre estenose aórtica e hemorragia gastrointestinal, seis décadas se passaram e não houve pouca controvérsia. Na época em que foi levantada, o estado técnico e metodológico da ciência médica e uma interpretação tendenciosa de sua ideia original impediram a construção de um apoio estatístico e fisiopatológico que lhe concederia amplo reconhecimento como entidade clínica individual. Avanços em diversas disciplinas permitiram demonstrar que sua frequência de apresentação excede o efeito do acaso, além de esclarecer com precisão e elegância seus mecanismos fisiopatológicos. Sua consolidação como síndrome revela uma verdadeira encruzilhada entre Cardiologia, Gastroenterologia, Hematologia e Laboratório, especialidades envolvidas tanto em seu processo de compreensão quanto em sua gestão prática hoje. No entanto, apesar de ter uma incidência não desprezível e adquirir um papel central no manejo clínico da estenose aórtica, esta entidade parece ter passado de resistida para relativamente ignorada. Com o intuto de contribuir para sua visibilidade, esta revisão oferece um panorama abrangente do tema, revendo as principais contribuições históricas ao seu conhecimento e abordando em profundidade seus mecanismos, as chaves para sua detecção clínica e seu impacto na gestão da estenose aórtica e outras entidades com fisiopatologia relacionada.

Respuesta a la prueba de desmopresina: estudio de cohorte en un hospital de Bogotá / Response to the desmopressin test: cohort study in a Bogota hospital

Introducción: La desmopresina es un análogo sintético de la vasopresina que aumenta los niveles plasmáticos del factor VIII y del factor de von Willebrand. Algunos autores señalan el tiempo de mantenimiento del efecto hemostático entre 6 y 8 h, por lo que es necesario estudiar su efecto en el tiempo. Objetivo: Determinar la variación de las variables de laboratorio de pacientes con enfermedad de von Willebrand y hemofilia tipo A posterior a la administración de desmopresina. Métodos: Estudio de cohorte retrospectivo en un hospital universitario en Bogotá. Se realizó un muestreo no aleatorio, se incluyeron 24 pacientes mayores de 18 años con diagnóstico de enfermedad de von Willebrand (67 por ciento) y hemofilia tipo A no grave (33 por ciento), a quienes se les realizó la prueba de desmopresina. Se conformaron dos grupos de pacientes, independientemente del diagnóstico: 15 pacientes con valores basales de factor VIII ; 50 UI y 13 pacientes con valores basales de antígeno von Willebrand lt; 50 UI. Se efectúo análisis estadístico descriptivo y correlacional en Stata 13. Resultados: El 87 por ciento de los pacientes del grupo I alcanzó el valor terapéutico a las 2 h de administrada la desmopresina (p= 0,000), el cual se mantuvo hasta 6 h en el 77 por ciento (p= 0,000). En el grupo II el 92 por ciento logró el valor terapéutico en 2 h (p= 0,003), que continuó hasta las 6 h en el 83 por ciento (p= 0,000). Conclusiones: La respuesta a la administración de desmopresina fue máxima a las 2 h posteriores, cuando comenzó a disminuir progresivamente, pero mantuvo el efecto terapéutico. Aunque no se encontraron efectos adversos, existe variabilidad de respuesta entre pacientes(AU)

Introduction: Desmopressin is a synthetic analog for vasopressin that increases the plasma levels of factor VIII and of von Willebrand factor. Some authors indicate maintenance time of hemostatic effect between 6 and 8 hours, so it is necessary to study its effect over time. Objective: To determine the variation of laboratory variables in patients with von Willebrand disease and type A hemophilia after desmopressin administration. Methods: Retrospective cohort study carried out in a university hospital in Bogotá. Nonrandomized sampling was used, including 24 patients older than 18 years and with a diagnosis of von Willebrand disease (67 percent) and non-severe type A hemophilia (33 percent), who underwent the desmopressin test. Two groups of patients were created, regardless of diagnosis: 15 patients with baseline values of factor-VIII 8203; #8203;lower than 50 IU and 13 patients with baseline values of von Willebrand antigen8203;8203;lower than 50 IU. Descriptive and correlational statistical analysis was performed in Stata 13. Results: 87 percent of patients in group I reached the therapeutic value two hours after desmopressin administration (p=0.000), which was maintained for up to six hours in 77 percent (p=0.000). In group II, 92 percent achieved the therapeutic value in two hours (p=0.003), which continued until six hours in 83 percent (p=0.000). Conclusions: Response to desmopressin administration was maximum at two hours, when it began to decrease progressively, but maintained the therapeutic effect. Although no adverse effects were found, there is variability of response among patients(AU)

Oral Hygiene and Dentition Status in Patients with Congenital Hemorrhagic Disorders: A Comparative Study

Abstract Objective: To compare the status of oral hygiene and dentition in patients with congenital hemorrhagic disorders with their age-matched healthy counterparts. Also, the prevalence of fear of dentists/ dental treatment among these patients was assessed. Material and Methods: This study was performed on children and adults with von Willebrand disease (vWD), hemophilia (A or B), and healthy subjects. Oral health and dentition status was assessed using the simplified oral hygiene index (OHI-S), plaque index, and the decayed, missing, filled teeth (dmft/DMFT) index. One-way ANOVA test was employed to compare the oral hygiene and dentition status of subjects in the three groups. A p-value of <0.05 was considered statistically significant. Results: The DMFT score did not vary significantly between the groups (p>0.05). Higher OHI-S scores and a poor oral hygiene status was observed more in the hemophilia group than the vWD group and healthy controls. A total of 27.3% of the subjects in the vWD group, 18.2% of subjects in the hemophilia group, and no subjects in the healthy group had a fear of dentists or dental treatment. Conclusion: Subjects with vWD had a higher number of carious teeth when compared to the other groups. Poor oral hygiene status was observed in subjects with hemophilia.

El papel de la enfermedad de von Willebrand en la hemorragia uterina anormal / Von Willebrand Disease in Abnormal Uterine Bleeding

RESUMEN La hemorragia uterina anormal es un término empleado para las alteraciones en la regularidad, duración y/o volumen de sangrado menstrual y es considerada una causa común de consulta médica y en ocasiones supone un reto diagnóstico para el médico tratante. Dentro del abordaje de la etiología de dicha patología, las coagulopatías afectan alrededor del 13 por ciento de las mujeres, y la más común es la enfermedad de von Willebrand. El objetivo de este trabajo fue realizar una revisión de la literatura científica actual sobre el papel que cumple la enfermedad de von Willebrand en la hemorragia uterina anormal. Esta es una patología hereditaria derivada de una deficiencia del factor von Willebrand encargado de la adhesión plaquetaria. La prevalencia de esta enfermedad puede ser baja, sin embargo, cuando se estudia la población de mujeres con menorragia, la frecuencia puede ir de 5 a 20 por ciento. Se han descrito diferentes problemas ginecológicos asociados a la enfermedad de von Willebrand, tales como menorragia, dismenorrea y una importante deficiencia de hierro asociada a esta, además de una mayor incidencia de quistes ováricos, endometriosis, hiperplasia endometrial y pólipos endometriales. La literatura actual sugiere que se realice tamizaje a aquellas mujeres con cuadro clínico sugestivo. Con respecto al tratamiento la literatura reporta el uso de ácido tranexámico y anticonceptivos orales, pero el que mayor utilidad ha demostrado es la desmopresina(AU)

ABSTRACT Abnormal uterine bleeding is a term used for alterations in the regularity, duration and / or volume of menstrual bleeding and it is considered a common cause of medical consultation; sometimes it is a diagnostic challenge for the treating physician. Within the aetiology approach of said pathology, coagulopathies affect around 13 percent of women, and the most common is von Willebrand disease. The objective is to review the current scientific literature on the influence of von Willebrand disease in abnormal uterine bleeding. This is an inherited pathology derived from a deficiency of the von Willebrand factor responsible for platelet adhesion. The prevalence of this disease may be low, however, when studying the population of women with menorrhagia, the frequency can range from 5 to 20 percent. Different gynecological problems associated with von Willebrand disease have been described, such as menorrhagia, dysmenorrhea and a significant iron deficiency associated with it, in addition to a higher incidence of ovarian cysts, endometriosis, endometrial hyperplasia and endometrial polyps. The current literature suggests that those women with suggestive clinical symptoms should be screened. Regarding treatment, the literature reports the use of tranexamic acid and oral contraceptives, nonetheless desmopressin has proven to be most useful(AU)

Perfil demográfico y epidemiológico de pacientes con Hemofilia y von Willebrand atendidos en el Área de Estomatología del Hospital de Especialidades Carlos Andrade Marín / Demographic and epidemiological profile of patients with Hemophilia and von Willebrand treated in the Stomatology Area of the Carlos Andrade Marín Specialties Hospital

INTRODUCCIÓN. Las alteraciones hereditarias de la hemostasia son patologías raras, dentro de estas se encuentran: Hemofilia A, Hemofilia B y von Willebrand. La hemofilia es un trastorno hereditario, ligado al cromosoma X, causado por ausencia o actividad reducida del factor VIII o IX. La enfermedad de von Willebrand es causada por la deficiencia del factor VIII. OBJETIVO. Determinar el perfil demográfico y epidemiológico de pacientes con Hemofilia y von Willebrand. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, transversal. La población de estudio fueron 133719 con una muestra de 144 pacientes, los criterios de inclusión fueron: pacientes de ambos sexos entre 2 a 88 años de edad, con diagnóstico de Hemofilia A, B, von Willebrand. Atendidos en la consulta externa del Área de Estomatología del Hospital de Especialidades Carlos Andrade Marín, en el periodo 2015-2018. Datos obtenidos del sistema AS400, analizados en el programa International Business Machines Statistical Package for the Social Sciences, Versión 22.0. RESULTADOS. El 77,0% (111; 144) perteneció al género masculino. El rango de edad fue entre 23 y 33 años con 24,0% (34; 144). Tuvieron Hemofilia A 62,0% (93; 144); Hemofilia B 6,0% (9; 144); von Willerbrand 28,0% (42; 144). El 50,0% (77; 144) recibieron tratamientos odontológicos; preventivos 15,0% (21; 144) y curativos 13,0% (18; 144); siendo la mayor patología caries dental. CONCLUSIÓN. Se determinó el perfil demográfico y epidemiológico de los pacientes con Hemofilia y von Willebrand que permitió brindar un tratamiento integral, interdisciplinario y oportuno.

INTRODUCTION. Hereditary abnormalities of hemostasis are rare pathologies, within these are: Hemophilia A, Hemophilia B and von Willebrand. Hemophilia is an inherited disorder, linked to the X chromosome, caused by absence or reduced activity of factor VIII or IX. Von Willebrand's disease is caused by factor VIII deficiency. OBJECTIVE. Determine the demographic and epidemiological profile of patients with hemophilia and von Willebrand. MATERIALS AND METHODS. Observational, descriptive, cross-sectional study. The study population was 133719 with a sample of 144 patients, the inclusion criteria were: patients of both sexes between 2 and 88 years of age, with a diagnosis of Hemophilia A, B, von Willebrand. Attended in the external consultation of the Stomatology Area of the Carlos Andrade Marín Specialty Hospital, in the period 2015-2018. Data obtained from the AS400 system, analyzed in the International Business Machines Statistical Package for the Social Sciences program, Version 22.0. RESULTS 77,0% (111; 144) belonged to the male gender. The age range was between 23 and 33 years with 24,0% (34; 144). They had hemophilia at 62,0% (93; 144); Hemophilia B 6,0% (9; 144); von Willerbrand 28,0% (42; 144). 50,0% (77; 144) received dental treatments; preventive 15,0% (21; 144) and curative 13,0% (18; 144); being the biggest dental caries pathology. CONCLUSION. The demographic and epidemiological profile of patients with Hemophilia and von Willebrand was determined, which allowed to provide a comprehensive, interdisciplinary and timely treatment.

A Multicenter Study on von Willebrand Disease Realities in Yeungnam Region / 임상소아혈액종양

BACKGROUND: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. However, the number of patients who register to the Korea Hemophilia Foundation (KHF) is much lower than the expected prevalence rate and only few hospitals perform tests for diagnosis autonomously. Thus, we surveyed practical realities of VWD in Yeungnam region. METHODS: Patients with VWD (N=267) who were diagnosed at eleven university hospitals from March 1995 to March 2018 were enrolled in this study. We evaluated the medical records from each hospital retrospectively. RESULTS: Two hundred and twenty-eight children and 39 adults met the diagnostic criteria for VWD. Seventy-eight (57.4%) patients had the blood type O. Fifty-eight patients were definite type 1 (21.7%), 151 were possible type 1 (56.6%), and the others were type 2. Abnormal laboratory findings were the most common factor for the diagnosis in children. VWF mutations were detected in 17 patients. Patients with a family history showed age of diagnosis of 9 y, which is higher than in those with no family history (6 yr), and also showed a higher rate of significant bleeding (32.1% vs. 14.2%). VWF:RCo and VWF:Ag tests were performed in-hospital at only 1 of 11 hospitals. Twelve of 267 patients were enrolled at the KHF (4.5%). CONCLUSION: A high rate of out-sourcing studies may result in inaccurate diagnosis. The registration rate to the KHF is still lower than the prevalence rate. A comprehensive nationwide registration system is necessary in order to identify the actual prevalence rate and promote the diagnosis of VWD in Korea.

Molecular Genetics of von Willebrand Disease in Korean Patients: Novel Variants and Limited Diagnostic Utility of Multiplex Ligation-Dependent Probe Amplification Analyses

BACKGROUND: von Willebrand disease (VWD), characterized by quantitative or qualitative defects of von Willebrand factor (VWF), is the most common inheritable bleeding disorder. Data regarding the genetic background of VWD in Korean patients is limited. To our knowledge, this is the first comprehensive molecular genetic investigation of Korean patients with VWD. METHODS: Twenty-two unrelated patients with VWD were recruited from August 2014 to December 2017 (age range 28 months–64 years; male:female ratio 1.2:1). Fifteen patients had type 1, six had type 2, and one had type 3 VWD. Blood samples were collected for coagulation analyses and molecular genetic analyses from each patient. Direct sequencing of all exons, flanking intronic sequences, and the promoter of VWF was performed. In patients without sequence variants, multiplex ligation-dependent probe amplification (MLPA) was performed to detect dosage variants. We adapted the American College of Medical Genetics and Genomics guidelines for variant interpretation and considered variants of uncertain significance, likely pathogenic variants, and pathogenic variants as putative disease-causing variants. RESULTS: VWF variants were identified in 15 patients (68%): 14 patients with a single heterozygous variant and one patient with two heterozygous variants. The variants consisted of 13 missense variants, one small insertion, and one splicing variant. Four variants were novel: p.S764Efs*16, p.C889R, p.C1130Y, and p.W2193C. MLPA analysis in seven patients without reportable variants revealed no dosage variants. CONCLUSIONS: This study revealed the spectrum of VWF variants, including novel ones, and limited diagnostic utility of MLPA analyses in Korean patients with VWD.

Establishment of Flow Cytometric Immunobead Array for Detecting Plasma Von Willebrand Factor Activity and Its Clinical Application in the Prognosis of Ischemic Stroke / 中国实验血液学杂志

OBJECTIVE@#To establish a novel flow cytometric immunobead array (FCIA) for detecting plasma von Willebrand factor activity (vWF:GPIbR) and apply it in ischemic stroke (IS).@*METHODS@#Microspheres coated with anti-human platelet glycoprotein Ibα (GPIbα) monoclonal antibody SZ151 IgG, were incubated with recombinant fragment of GPIbα, then added ristocetin and plasma, finally incubated with FITC-conjugated sheep-anti-human vWF IgG polyclonal antibody, and detected by flow cytometry. vWF antigen (vWF:Ag), vWF:GPIbR, and vWF collagen binding assay (vWF:CB) were also included for evaluating vWF levels in IS patients.@*RESULTS@#The intra-assay coefficient variations (CVs) and inter-assay CVs of FCIA were 7.7% and 13.5%, respectively. The slope of the linear regression was 0.9739 (r=0.855, P<0.001), and the Bland-Altman bias was 9.95%, indicating a good correlation between FCIA and ELISA. The FCIA had better sensitivity, specificity and accuracy as compared with those by ELISA (P<0.05). The levels of vWF:Ag, vWF:GPIbR and vWF:CB in IS patients were significantly higher in comparison with those in healthy controls (H=7.8, 6.4, 6.2, respectively, P<0.01), the level of vWF:GPIbR in IS patients positively correlated with levels of vWF:Ag, high-sensitivity C-reactive protein, Autar score and hospitalization time.@*CONCLUSION@#The FCIA for detecting plasma vWF:GPIbR is more specific and accurate than ELISA. The vWF:GPIbR is involved in the paroxysm of IS, which could be used to evaluate the risk of thrombosis in IS patients.

Móleculas protrombóticas en niños con Diabetes Mellitus Tipo 1 / Study of prothrombotic molecules in type 1 diabetes mellitus children

Introducción: la hiperglucemia contribuye a cambios moleculares que alteran la hemostasia. Objetivos: determinar moléculas circulantes que indiquen la presencia de un estado protrombótico en una población infanto juvenil con diabetes mellitus tipo 1 (DM1), sin manifestación clínica de enfermedad vascular, y compararla con una población control. Pacientes y métodos: se estudiaron 35 pacientes con DM1, de 11,0±2,5 años de edad y 3,7±2,0 años de evolución de la enfermedad, sin complicaciones vasculares y 20 controles sanos de edad, sexo e IMC semejantes. Se determinaron: fibrinógeno (Fg), inhibidor del activador del plasminógeno 1 (PAI-1), antígeno del factor von Willebrand (FvW:Ag), ligando CD40 soluble (sCD40L) y pruebas globales de coagulación como recuento de plaquetas, tiempo de protrombina (TP) y tiempo de tromboplastina parcial activado (APTT). El control glucémico se evaluó mediante glucemia en ayunas y A1c, y se descartó la presencia de retinopatía y nefropatía. Los datos se analizaron con el programa SPSS 20 para Windows y se expresaron como media±DE. El coeficiente de Pearson se usó para investigar las correlaciones entre las variables estudiadas. Resultados: los pacientes con DM1 presentaron valores significativamente mayores de Fg (308±66 vs 246±18 mg/dL, p=0,0001), PAI-1 (41,6±12 vs 11,7±1,0 ng/mL, p=0,0001), FvW:Ag (284±55 vs 121±19 %, p=0,0001) y sCD40L (1608±109 vs 149±17 pg/mL, p=0,0001). Sin embargo las pruebas globales de hemostasia no mostraron diferencias entre ambos grupos. El PAI-1 y sCD40L se correlacionaron con glucemia, A1c, Fg y FvW:Ag. Conclusiones: los niveles elevados de Fg, PAI-1, FvW:Ag y sCD40L sugieren la presencia de un estado protrombótico en la población infanto juvenil con DM1

Introduction: hyperglycemia contributes to molecular changes that alter hemostasis. Objectives: to determine molecules of a prothrombotic state in a child-juvenile population with type 1 diabetes (T1D), without clinical manifestation of vascular disease, and compare it with a control population. Patients and methods: thirty-five patients with T1D (11.0±2.5 years and 3.7±2.0 years of disease duration), without vascular complications and 20 healthy controls were studied. Plasma fibrinogen (Pf), plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor antigen vWF:Ag and soluble CD40 ligand (sCD40L) and coagulation global tests such as platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) were determined. The data obtained were analized by Statistics SPSS 20 software and were expressed as the mean±standard desviation. Pearson coefficient was used to investigate correlations between variables. Results: diabetic patients presented significantly higher values of glycaemia, A1c, Fg (308± 66 vs 246±18 mg/dL, p=0.0001), PAI-1 (41.6±12 vs 11.7±1, 0 ng/mL, p=0.0001), vWF:Ag (284±55 vs 121±19%, p= 0.0001) and sCD40L (1608±109 vs 149±17 pg/mL, p=0.0001). However, overall hemostasis tests showed no differences between both groups, PAI-1 and sCD40L correlated with glycemia, A1c, Fg and vWF:Ag. Conclusions: high levels of Fg, PAI-1, vWF:Ag and sCD40L suggest the presence of a prothrombotic state in the infant population juvenil with DT1

Tuberculosis anal como diagnóstico diferencial de lesión ulcerada anal / Anal tuberculosis as a differential diagnosis of ulcerated anal lesion

La tuberculosis (TBC) es una enfermedad infecciosa crónica, granulomatosa, transmisible, producida por el microorganismo Mycobacterium tuberculosis o bacilo de Koch. Puede presentarse como enfermedad pulmonar, extrapulmonar o ambas. La presentación extrapulmonar, es rara, representando aproximadamente el 11% de todos los casos. El objetivo del presente trabajo es comunicar un caso clínico de tuberculosis de localización extrapulmonarr infrecuente: la región perianal. (AU)

Tuberculosis (TB) is a chronic infectious, granulomatous, transmissible disease produced by the Mycobacterium tuberculosis microorganism or Koch's bacillus.It can present as lung disease, extrapulmonary disease or both.Extrapulmonary presentation is rare, representing approximately 11% of all cases. The objective of the present work is to report a clinical case of tuberculosis of uncommon extrapulmonary location: the perianal region. (AU)

Conocimiento acerca de la enfermedad de Von Willebrand entre estudiantes de Odontología / Knowledge about von Willebrand's disease among dental students

Introduction: Von Willebrand's disease is the most common bleeding disorder, and is still underdiagnosed for several reasons, including lack of knowledge about the disease. Objective: to evaluate the knowledge about dental care for patients with von Willebrand's disease in students who attended the last academic year of an undergraduate dental program. Methods: a questionnaire with objective questions was applied to 87 students in order to obtain data on the following variables of interest: gender, term of the program, knowledge about the disease, knowledge about the involved coagulation factor, tests for diagnosis, signs and symptoms, procedures necessary during patient care, and medications that should be avoided in von Willebrand's disease. The data were analyzed using IBM SPSS (21.0) at a significance level of 5 percent. Results: only 21 students (21.14 percent) reported having some knowledge about von Willebrand's disease: 49.02 percent correctly answered that the coagulation factor is involved in von Willebrand's disease, and 29.4 percent correctly answered to the question about the diagnostic tests. Conclusions: students attending the final academic year of an undergraduate dental program have limited knowledge about von Willebrand's disease(AU)

Introducción: la enfermedad de Von Willebrand es el trastorno hemorrágico más común, y todavía está infradiagnosticada por varias razones, incluyendo la falta de conocimiento acerca de la enfermedad. Objetivo: evaluar el conocimiento acerca del cuidado dental para pacientes con la enfermedad de Von Willebrand en los estudiantes que asistieron al último año de un programa de odontología de pregrado. Métodos: se aplicó un cuestionario con preguntas objetivas a 87 estudiantes para obtener datos sobre las siguientes variables de interés: género, término del programa, conocimiento acerca de la enfermedad, conocimiento sobre el factor de coagulación implicado, pruebas para el diagnóstico, signos y síntomas, procedimientos necesarios durante el cuidado de pacientes y los medicamentos que deben evitarse en la enfermedad de Von Willebrand. Los datos fueron analizados utilizando IBM SPSS (21.0) a un nivel de significación del 5 por ciento. Resultados: solo 21 estudiantes (21,14 por ciento) reportaron tener algún conocimiento sobre la enfermedad de Von Willebrand: 49,02 por ciento respondió correctamente cuál es el factor de coagulación que está involucrado en enfermedad de Von Willebrand, y el 29,4 por ciento respondió correctamente a la pregunta sobre las pruebas diagnósticas. Conclusiones: los estudiantes que asisten al último año de un programa de odontología de grado tienen un conocimiento limitado acerca de la enfermedad de Von Willebrand(AU)

A Multicenter Study on Korean von Willebrand Disease Realities / 임상소아혈액종양

BACKGROUND: von Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of up to 1%. However in Korea, only 126 VWD patients were registered in Korea Hemophilia Foundation (KHF). The aim of this study was to determine the status of VWD patients in Korea. We analyzed VWD patients by age, gender, blood group, family history and bleeding history.METHODS: One hundred twenty-six VWD patients registered in the KHF by December 2016, and 74 patients diagnosed at six university hospitals were enrolled in this study. We evaluated the medical records from the KHF and the questionnaires from six university hospitals retrospectively.RESULTS: Seventeen patients misdiagnosed and ten patients duplicated were excluded. One hundred nine patients registered in the KHF and 64 patients diagnosed at six university hospitals met the criteria for VWD. The blood type O accounts for 72 (51.8%). VWF mutation was detected in 30 patients (17.3%). Median age at diagnosis was 10.5 yr. The bleeding score of adults was higher than that of children (P < 0.001). The most common bleeding symptom was epistaxis (48.5%). The distribution of VWD types was: 67% of type 1, 30.1% of type 2, and 2.9% of type 3.CONCLUSION: Even though only six hospitals responded to the survey, 64 patients not registered in the KHF were diagnosed with VWD. Our results suggest the prevalence of Korean VWD might be higher than previously reported. A nationwide registration system is warranted in order to accurately identify the national prevalence of VWD.

Surgery in Patients with Von Willebrand Disease : A Single Center Experience / 임상소아혈액종양

BACKGROUND: Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Surgery, even relatively minor procedures, in patients with moderate to severe qualitative and quantitative deficiencies of von Willebrand factor (VWF) can be associated with a life-threatening risk of excessive bleeding. The purpose of this study was to evaluate the safety and efficacy of VWF/FVIII in patients with von Willebrand disease before surgery and determine the efficacy of VWF/FVIII.METHODS: We reviewed the results of surgical procedures in patients with VWD at Kyung Hee University Hospital at Gangdong, between September 2009 and January 2016. VWF/FVIII concentrates were administrated preoperatively to all patients.RESULTS: Between September 2009 and January 2016 at our center, eight surgical procedures were performed successfully and no severe complications were observed in the seven patients with VWD. Four orthopedic procedures, one laparoscopic appendectomy, one ovary cystectomy, one strabotomy, and one dental extraction were performed. The median duration of hospitalization was seven days. VWF/FVIII concentrates were administered prior to all procedures, including the dental extraction. In all cases, uncontrolled bleeding and thromboembolic complications were not observed.CONCLUSION: Patients with VWD who require surgery can be treated efficiently and safely with VWF/FVIII concentrates. There is excellent tolerance, efficacy and safety in preventing excessive bleeding during surgery. When administering VWF/FVIII concentrates, treatment should be monitored with VWF Ag, VWF:RCo and FVIII plasma levels.