Evaluación de la hemostasia en niños con Síndrome de Ehlers-Danlos tipo III / Hemostasis evaluation in children with type III Ehlers-Danlos syndrome

Introducción: Aunque no se ha demostrado la existencia de alteraciones de la hemostasia que formen parte del cuadro clínico del síndrome de Ehlers-Danlos, se han reportado diversas alteraciones de la coagulación en casos aislados, como son eficiencia y alteraciones de la movilidad electroforética de la fibronectina, disfunción de la agregación plaquetaria con prolongación del tiempo de sangramiento, deficiencia de factores VIII, IX, XII y XIII y aumento de la sensibilidad a la aspirina, entre otras. Objetivo: Evaluar la existencia de alteraciones de la hemostasiaen niños con síndrome de Ehlers-Danlos tipo III. Métodos: Se realizó una investigación aplicada, observacional, descriptiva y transversal en 305 niños con síndrome de Ehlers-Danlos tipo III para evaluar, en aquellos con historia de manifestaciones hemorrágicas, la existencia de alteraciones de la hemostasia.Previa suspensión de drogas con acción antiagregante plaquetaria, a todos los pacientes se les realizaron estudios decoagulación y función y agregación plaquetaria. Resultados: En 181 pacientes se encontró historia de sangramiento espontáneo o traumático, predominantemente cutáneo-mucoso. Elcoagulograma fue normal en todos los casos y el extendido de sangre periférica mostró la presencia de macroplaquetas y escasa formación de grumos como alteración frecuente. Las pruebas de agregación y función plaquetaria evidenciaron la existencia de trastornos cualitativos con predominio de la disminución de la agregación con ADP, sola o combinada con epinefrina y colágeno, y con menor frecuencia trastornos de la disponibilidad de los fosfolípidos plaquetarios. La mayoría de estos pacientes habían utilizado antihistamínicos (ketotifeno) por diversas causas. Conclusiones: Se reporta la presencia de defectos cualitativos plaquetarios en niños con síndrome de Ehlers-Danlos tipo III destacándose el papel de la utilización de drogas antihistamínicas en la aparición de manifestaciones hemorrágicas en estos pacientes(AU)

Introduction: Although the existence of hemostasis disorders as part of type-III Ehlers-Danlos syndrome has not been confirmed, several coagulation alterations have been reported in isolated cases such as: deficiencies and modification in electrophoresis mobility of fibronectin, dysfunction of platelet aggregation with lengthening of bleeding time, deficiency of VIII, IX, XII and XIII factors and increase of aspirin sensitivity, among others. Objective: Evaluate the existence of hemostasis disorders in children with type III Ehlers-Danlos syndrome. Method: an applied, observational, descriptive and cross-sectional research was carried out in 305 children suffering from type-III Ehlers_Danlos syndrome to evaluate in those having history of hemorrhagic manifestations, the existence of alterations of the hemostasis. Previous suspension of drugs with platelet anti-aggregation action, coagulation and platelet aggregation function studies were carried out. Results: The study revealed that 181 patients presented history of spontaneous or traumatic bleeding mainly mucous-cutaneous. Coagulogram was normal in all cases and peripheral-blood smears showed the presence of macro-platelets and deficient formation of clots as the most frequent alteration. Aggregation and platelet function tests evidenced the presence of qualitative disorders, where a decrease of aggregation prevailed with the use of adenosine diphosphate (ADP), alone or combined with epinephrine and collagen, and with less frequency, disorders of of platelet phospholipids availability. The majority of these patients presented history of long-lasting use of antihistamines (ketotifen) due to diverse causes. Conclusions: The occurrence of these qualitative platelet defects in children with EDS-type III is reported, standing out the role of the use of antihistamine drugs on the onset of the hemorrhagic symptoms in these patients(AU)

Evaluación de la hemostasia en niños con Síndrome de Ehlers-Danlos tipo III / Hemostasis evaluation in children with type III Ehlers-Danlos syndrome

Introducción: Aunque no se ha demostrado la existencia de alteraciones de la hemostasia que formen parte del cuadro clínico del síndrome de Ehlers-Danlos, se han reportado diversas alteraciones de la coagulación en casos aislados, como son eficiencia y alteraciones de la movilidad electroforética de la fibronectina, disfunción de la agregación plaquetaria con prolongación del tiempo de sangramiento, deficiencia de factores VIII, IX, XII y XIII y aumento de la sensibilidad a la aspirina, entre otras. Objetivo: Evaluar la existencia de alteraciones de la hemostasiaen niños con síndrome de Ehlers-Danlos tipo III. Métodos: Se realizó una investigación aplicada, observacional, descriptiva y transversal en 305 niños con síndrome de Ehlers-Danlos tipo III para evaluar, en aquellos con historia de manifestaciones hemorrágicas, la existencia de alteraciones de la hemostasia.Previa suspensión de drogas con acción antiagregante plaquetaria, a todos los pacientes se les realizaron estudios decoagulación y función y agregación plaquetaria. Resultados: En 181 pacientes se encontró historia de sangramiento espontáneo o traumático, predominantemente cutáneo-mucoso. Elcoagulograma fue normal en todos los casos y el extendido de sangre periférica mostró la presencia de macroplaquetas y escasa formación de grumos como alteración frecuente. Las pruebas de agregación y función plaquetaria evidenciaron la existencia de trastornos cualitativos con predominio de la disminución de la agregación con ADP, sola o combinada con epinefrina y colágeno, y con menor frecuencia trastornos de la disponibilidad de los fosfolípidos plaquetarios. La mayoría de estos pacientes habían utilizado antihistamínicos (ketotifeno) por diversas causas. Conclusiones: Se reporta la presencia de defectos cualitativos plaquetarios en niños con síndrome de Ehlers-Danlos tipo III destacándose el papel de la utilización de drogas antihistamínicas en la aparición de manifestaciones hemorrágicas en estos pacientes

Introduction: Although the existence of hemostasis disorders as part of type-III Ehlers-Danlos syndrome has not been confirmed, several coagulation alterations have been reported in isolated cases such as: deficiencies and modification in electrophoresis mobility of fibronectin, dysfunction of platelet aggregation with lengthening of bleeding time, deficiency of VIII, IX, XII and XIII factors and increase of aspirin sensitivity, among others. Objective: Evaluate the existence of hemostasis disorders in children with type III Ehlers-Danlos syndrome. Method: an applied, observational, descriptive and cross-sectional research was carried out in 305 children suffering from type-III Ehlers_Danlos syndrome to evaluate in those having history of hemorrhagic manifestations, the existence of alterations of the hemostasis. Previous suspension of drugs with platelet anti-aggregation action, coagulation and platelet aggregation function studies were carried out. Results: The study revealed that 181 patients presented history of spontaneous or traumatic bleeding mainly mucous-cutaneous. Coagulogram was normal in all cases and peripheral-blood smears showed the presence of macro-platelets and deficient formation of clots as the most frequent alteration. Aggregation and platelet function tests evidenced the presence of qualitative disorders, where a decrease of aggregation prevailed with the use of adenosine diphosphate (ADP), alone or combined with epinephrine and collagen, and with less frequency, disorders of of platelet phospholipids availability. The majority of these patients presented history of long-lasting use of antihistamines (ketotifen) due to diverse causes. Conclusions: The occurrence of these qualitative platelet defects in children with EDS-type III is reported, standing out the role of the use of antihistamine drugs on the onset of the hemorrhagic symptoms in these patients

Vascular Ehlers-Danlos syndrome: pathophysiology, diagnosis, and prevention and treatment of its complications.

The Ehlers-Danlos syndrome consists of a group of inherited connective tissue disorders caused by defects in the synthesis of collagen. The vascular type 4 form of Ehlers-Danlos syndrome (VEDS) is associated with serious vascular complications in young adults, such as the spontaneous rupture of large-caliber and medium-caliber arteries, often without true aneurysm formation or dissection. VEDS is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene. It affects the synthesis and structure of the pro a1 (III) chain of collagen type III, which causes vascular wall weakness. The diagnosis of VEDS is made from major and minor clinical criteria and can be confirmed by abnormalities in procollagen production and molecular genetic testing. Recently, the results of a study using the b-blocker celiprolol demonstrated a reduction in vascular complications of VEDS. The mechanisms of benefit may be related to a reduction in vascular hemodynamic stress with exercise and/or through a reduction in transforming growth factor-b. Inhibitors of the renin-angiotensin system may also be beneficial in VEDS. Surgery may be beneficial in treating the complications of VEDS.

A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin.

Preterm premature rupture of membranes is responsible for one-third of preterm births. Ehlers-Danlos syndrome (EDS) is associated with preterm premature rupture of membranes in humans. In particular, an EDS variant is caused by a genetic mutation resulting in abnormal secretion of biglycan and decorin, two small leucine-rich proteoglycans highly expressed in reproductive tissues. Because biglycan/decorin null mutant (Bgn(-/-)Dcn(-/-)) mice demonstrate phenotypic changes similar to EDS, we used this model to test whether either biglycan or decorin or both play a role in the attainment of successful term gestation. Wild-type biglycan null mutant, decorin null mutant, and biglycan/decorin null mutant pregnancies were assessed for the length of gestation, pup and placenta weight, and litter size. Quantitative real-time PCR was performed to measure biglycan and decorin gene expression, and immunohistochemistry was performed to assess protein expression in placenta and fetal membranes at embryonic days E12, E15, and E18. Bgn(-/-)Dcn(-/-) dams displayed preterm birth, whereas the possession of at least two biglycan or decorin wild-type alleles was protective of preterm birth. The number of Bgn(-/-)Dcn(-/-) pups was decreased at postnatal day P1 but not at E18. Biglycan and decorin were upregulated in the placenta in the absence of each other and were developmentally regulated in fetal membranes, suggesting that these two proteoglycans demonstrate genetic complementation and contribute to gestational success in a dose-dependent manner. Thus, the biglycan/decorin null mutant mouse is a model of genetically induced preterm birth and perinatal loss. This model presents novel targets for preventive or therapeutic manipulation of preterm birth.