Perioperative administration of recombinant activated factor VII in a Glanzmann's thrombasthenia patient with platelet refractoriness: case report

Abstract Glanzmannʼs Trombasthenia (GT) is a genetic disorder, that develops with a tendency toward bleeding and is characterized by the absence or decrease in platelet aggregation. Surgical bleeding may be difficult to control. Platelet transfusion is the main treatment, albeit refractoriness can occur. We describe the case of a patient with GT and platelet refractoriness, who was submitted to radical prostatectomy and dental extraction. The perioperative treatment with apheresis platelet concentrate and activated recombinant factor seven allowed the procedures to be performed uneventfully. We discuss the complexity of the case and the treatment option.

Manejo de la trombastenia de Glanzmann durante el embarazo: reporte de un caso y revisión de la literatura / Management of Glanzmann's thrombasthenia during pregnancy: a case report and literature review

Resumen Objetivo: Reportar el caso de una paciente con trombastenia de Glanzmann que recibe manejo con transfusión de plaquetas con factor VII activado y realizar una revisión de la literatura referente al tratamiento y el pronóstico de esta patología durante la gestación. Método: Se presenta el caso de una paciente de 27 años con trombastenia de Glanzmann y embarazo de 33 semanas, con cesárea al término sin complicaciones. Se realizó una búsqueda en las bases de datos Medline vía PubMed, Lilacs, SciELO y ScienceDirect; se incluyeron reportes de caso, series de casos y revisiones bibliográficas hasta 2021. Resultados: Se encontraron 21 artículos, con 23 casos reportados. Los embarazos se presentaron entre la tercera y la cuarta décadas de la vida, siendo la mayoría pacientes con anticuerpos frente a antígenos plaquetarios (43,4% de los casos). El principal manejo fue con transfusión plaquetaria. Conclusiones: La trombastenia de Glanzmann durante el embarazo es infrecuente y se asocia a eventos hemorrágicos. La presencia de anticuerpos frente a antígenos plaquetarios condiciona el manejo con mayor riesgo de complicaciones perinatales. No tiene un enfoque terapéutico unificado, siendo el de elección la transfusión de plaquetas y como segunda línea el factor VII activado.

Abstract Objective: To report the case of a patient with Glanzmann's thrombasthenia who receives management with platelet transfusion with activated factor VII and a literature review regarding the treatment and prognosis of this pathology during pregnancy. Method: We present the case of a 27 year old patient with Glanzmann's thrombasthenia and a 33-week pregnancy, with a cesarean section at term without complications. Medline databases were searched via PubMed, Lilacs, SciELO and ScienceDirect; case reports, case series and bibliographic reviews were included until 2021. Results: A total of 21 articles were found, with 23 reported cases; the pregnancies occurred between the third and fourth decades of life, the majority being patients with anti-platelet antigen antibodies in 43.4% of the cases. The main management was with platelet transfusion. Conclusions: Glanzmann's thrombasthenia during pregnancy is rare and is associated with hemorrhagic events. The presence of anti-platelet antigen antibodies conditions management with a higher risk of perinatal complications. It does not have a unified therapeutic approach, with platelet transfusion being the management of choice and activated factor VII as second line.

Expert opinion on the use of platelet secretion assay for the diagnosis of inherited platelet function disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology.

Assessment of platelet secretion is crucial for diagnosing suspected inherited platelet function disorders (IPFD). A previous survey of the SSC on Platelet Physiology of the ISTH and a comprehensive review highlighted that most of the platelet secretion assays (PSAs) lack standardization and validation. The aim of this study was to provide expert consensus guidance on the use of PSAs for IPFD diagnosis. We surveyed 26 experts from 10 different countries using the RAND/UCLA methodology, to attain a consensus on sensitivity, specificity, feasibility, time to readout, and cost of most PSAs. Answers were then graded in three categories: appropriate, uncertain, and inappropriate. Equivocal or misinterpretable statements required a second and third round survey involving 14 of the original 26 experts. We report here the consolidated results of the entire procedure. There was uniform agreement on several general statements, including that PSAs should be performed in hemostasis laboratories as first line diagnostic tests even in patients with normal platelet aggregation, and should include a δ-granule secretion marker. Among the specific assays examined, lumiaggregometry, other luciferin/luciferase-based assays, high-performance liquid chromatography methods, radiolabeled-serotonin based assays, and whole-mount transmission electron microscopy were rated as appropriate for the measurement of δ-granule release, and platelet P-selectin expression by flow cytometry and released proteins by ELISA for α-granule release. For most of the other PSAs, the expert opinions were widely dispersed. Lack of expert consensus on many PSAs clearly indicates an unmet need for rigorous standardization, multicenter comparison of results, and validation of PSAs for clinical laboratory practice.

High-power laser for periodontal surgery in a patient with glanzmann thrombasthenia / Laser de alta potência para cirurgia periodontal em paciente com trombastenia de glanzmann

Background: Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder characterized by platelet function impairment. Considering that the oral cavity is highly vascularized and performing some local hemostatic maneuvers may be difficult, GT patients are at high risk for hemorrhage related to invasive oral procedures. This study aimed to present an alternative method for periodontal surgery in a young GT patient. Case Report: A 15-year-old female GT patient with a recent history of excessive bleeding following dental surgeries was referred to a public dental center, presenting gingival hyperplasia. The procedure was performed using a high-power laser (HPL), and except for local anesthesia with epinephrine, no further hemostatic agent was necessary. Conclusion: According to the case, the HPL seems to be an efficient tool for preventing perioperative bleeding in GT patients submitted to minor oral surgeries(AU)

Introdução: A trombastenia de Glanzmann (TG) é uma doença autossômica recessiva rara caracterizada por comprometimento da função plaquetária. Tendo em vista que a cavidade oral é altamente vascularizada e a realização de algumas manobras hemostáticas locais pode ser difícil, pacientes com TG apresentam alto risco de hemorragia relacionada a procedimentos orais invasivos. Este artigo teve como objetivo apresentar uma técnica alternativa para cirurgia periodontal em um paciente jovem com TG. Relato de Caso: Paciente com TG, sexo feminino, 15 anos, com história recente de sangramento excessivo relacionado a cirurgias odontológicas prévias, foi encaminhada a um centro odontológico público apresentando hiperplasia gengival. O procedimento de remoção foi realizado com laser de alta potência e, com exceção da anestesia local com epinefrina, nenhum outro agente hemostático foi necessário. Conclusão: De acordo com o caso, o laser de alta potência parece ser uma ferramenta eficiente na prevenção de sangramento perioperatório em pacientes com TG submetidos a pequenas cirurgias orais(AU)

Perioperative administration of recombinant activated factor VII in a Glanzmann's thrombasthenia patient with platelet refractoriness: case report.

Glanzmann's Trombasthenia (GT) is a genetic disorder, that develops with a tendency toward bleeding and is characterized by the absence or decrease in platelet aggregation. Surgical bleeding may be difficult to control. Platelet transfusion is the main treatment, albeit refractoriness can occur. We describe the case of a patient with GT and platelet refractoriness, who was submitted to radical prostatectomy and dental extraction. The perioperative treatment with apheresis platelet concentrate and activated recombinant factor seven allowed the procedures to be performed uneventfully. We discuss the complexity of the case and the treatment option.

Perioperative considerations in a girl with Glanzmann thrombasthenia. Case report / Consideraciones perioperatorias en niña con trombastenia de Glanzmann. Reporte de caso

Abstract Introduction Glanzmann thromboasthenia is a rare congenital bleeding disorder caused by a mutation in platelet glycoprotein α-IIb and β3 encoding genes (ITGA2B; 607759 and ITGB3; 173470) in chromosomes I7q21.31 and 17q21.32, respectively, which results in a qualitative or quantitative alteration of the platelet integrin αIIbβ3 (glycoprotein IIb/IIIa) receptor. Glanzmann thromboasthenia is classified as type I when less than 5% of glycoprotein αIIbβ3 is expressed, and as type II when more than 5% is expressed. Case presentation Description of the perioperative management of a 13-year-old female patient with Glanzmann thromboasthenia who underwent endoscopic anterior bilateral ethmoidectomy. Management was centered on prophylactic platelet transfusion plus the use of tranexamic acid, as well as thromboelastographic determination of hemostasis. There were no bleeding complications during or after the procedure. Conclusiones Pediatric patients with Glanzmann thromboasthenia are at a high risk of perioperastive bleeding. Platelet transfusion is the best prophylactic and therapeutic alternative; however, even in the absence of anti-platelet antibodies, it may not be effective, and viscoelastic testing must be used for assessment during the surgical procedure in order to improve patient safety.

Resumen Introducción La trombastenia de Glanzmann es un trastorno hemorrágico congénito infrecuente, causado por mutación en los genes que codifican las glucoproteínas plaquetarias α-IIb (ITGA2B; 607759) y β3 (ITGB3; 173470) en los cromosomas I7q2i.3i y I7q2i.32, respectivamente, alterando cualitativa o cuantitativamente al receptor plaquetario de integrina αIIbβ3 (glucoproteína IIb/IIIa). La trombastenia de Glanzmann se clasifica como tipo I cuando se expresa menos del 5 % de la glucoproteína αIIbβ3 y como tipo II, cuando es mayor al 5 %. Presentación del caso Se describe el manejo perioperatorio de una paciente de 13 años de edad con trombastenia de Glanzmann, sometida a etmoidectomía anterior bilateral endoscópica. El manejo se centró en la transfusión profiláctica de plaquetas y ácido tranexámico, así como en la evaluación de la hemostasia con tromboelastografía. No hubo complicaciones hemorrágicas durante y después del procedimiento. Conclusiones Los pacientes pediátricos con trombastenia de Glanzmann tienen alto riesgo de hemorragia perioperatoria. La transfusión de plaquetas es la mejor alternativa profiláctica y terapéutica; sin embargo, incluso en ausencia de anticuerpos antiplaquetarios, puede no ser efectiva y debe evaluarse mediante pruebas viscoelásticas durante los procedimientos quirúrgicos para mejorar la seguridad del paciente.

Trombastenia de Glanzmann: conceptos clave de la enfermedad / Glanzmann thrombasthenia: key concepts of the disease

La trombastenia de Glanzmann (TG), es un trastorno autosómico recesivo en el cual hay una reducción grave o ausencia de la agregación plaquetaria. Se debe a las alteraciones cualitativas o cuantitativas de la integrina α IIb o de integrina β 3, codificados por los genes ITGA2B e ITGB3 y relacionadas con la glicoproteína IIb/IIIa, que intervienen en la activación plaquetaria. La mayor incidencia de TG ha sido reportada en la población judía-iraquí, pero también se ha presentado en Israel, Jordania, Arabia saudita, Italia y, en menor número, en familias gitanas y pakistaníes. A pesar de ser poco frecuente, este trastorno se debe sospechar en casos de trastornos hemorrágicos graves espontáneos o inducidos por traumatismos, que varían desde hemorragias gastrointestinales y mucocutáneas, como epistaxis y hemorragias gingivales recurrentes de difícil manejo, las cuales son potencialmente mortales y en más del 75 por ciento de los casos requieren transfusión sanguínea o plaquetaria. Para realizar la confirmación del diagnóstico, los hallazgos de laboratorio se caracterizan por tiempos de sangrado prolongados, retracción del coágulo disminuida y respuestas anormales de agregación plaquetaria a estímulos fisiológicos. Aunque, actualmente no existe una cura para la enfermedad, el tratamiento adecuado con transfusiones plaquetarias y en caso de refractariedad, el uso del factor VIIa, permiten un buen pronóstico para los pacientes. Aún queda mucho por estudiar en estos casos debido a esto se están realizando nuevos estudios para la posibilidad de otros tratamientos, entre ellos la terapia génica plaquetaria(AU)

Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder in which there is a severe reduction or absence of platelet aggregation. It is due to the qualitative or quantitative alterations of integrin #945; IIb or integrin #946; 3, encoded by the ITGA2B and ITGB3 genes and related to glycoprotein IIb / IIIa, which intervene in platelet activation. The highest incidence of GT has been reported in the Jewish-Iraqi population, but it has also been reported in Israel, Jordan, Saudi Arabia, Italy, and in smaller numbers in Gypsy and Pakistani families. Despite being uncommon, this disorder should be suspected in cases of severe spontaneous or trauma-induced bleeding disorders, ranging from gastrointestinal and mucocutaneous hemorrhages such as epistaxis and recurrent, difficult to manage gingival hemorrhages, which are potentially fatal and more than 75 percent of cases require blood or platelet transfusion. To confirm the diagnosis, the laboratory findings are characterized by prolonged bleeding times, decreased clot retraction and abnormal platelet aggregation responses to physiological stimuli. Although there is currently no cure for the disease, adequate treatments with platelet transfusions and in case of refractoriness, the use of factor VIIa, allow a good prognosis for patients. There is still much to study in these cases, because of this, new studies are being conducted for the possibility of other treatments, including platelet gene therapy(AU)

Unusual redo mitral valve replacement for bleeding in Glanzmann thrombasthenia.

We report the case of 23-year-old man with mitral valve regurgitation and Glanzmann thrombasthenia, who underwent mechanical mitral valve replacement. Warfarin therapy was devastating, causing bilateral hemothorax, pericardial effusion, gastrointestinal bleeding, and hematuria. Redo mitral valve replacement with a biological prosthesis was required to resolve this critical situation. To our knowledge, this is the first report of mitral valve replacement in Glanzmann thrombasthenia, highlighting the danger of oral anticoagulation in this pathology.

Manejo integral hematológico-odontológico en trombastenia de Glanzmann / Hematology-dental integrated management in Glanzmann thrombasthenia

La trombastenia de Glanzmann (TG) es una enfermedad hematológica de baja frecuencia, tiene un patrón de herencia autosómica recesiva. Se caracteriza por alteración de la función plaquetaria. Se puede presentar como petequias, epistaxis, hemorragias gastrointestinales y gingivales. Se reporta el caso de un paciente de género masculino que acude a servicio odontológico universitario anexo a hospital de cuarto nivel por presentar gingivorragia severa y aflojamiento de algunos dientes. El manejo integral del paciente muestra la importancia del trabajo multidisciplinario. (Acta Med Colomb 2015; 40: 58-61).

Glanzmann's thrombasthenia (GT) is a low frequency hematologic disease with an autosomal recessive inheritance pattern. It is characterized by impaired platelet function. It It can occur as petechiae, epistaxis and gastrointestinal and gingival bleeding. The case of a male patient who attends University Dental Service annex to fourth level hospital for presenting severe gingival bleeding and loosening of some teeth is reported. The integral management of the patient shows the importance of multidisciplinary work. (Acta Med Colomb 2015; 40: 58-61).

Conduta no perioperatório de paciente pediátrico com trombastenia de glanzmann durante adenoidectomia / Perioperative management of a pediatric patient with glanzmann's thrombasthenia during adenoidectomy / Conducta en el perioperatorio de paciente pediátrico con trombastenia de glanzmann durante la adenoidectomía

JUSTIFICATIVA E OBJETIVOS: Trombastenia de Glanzmann (TG) é uma doença autossômica recessivamente hereditária das plaquetas. Não há nenhum tratamento específico. A transfusão de plaquetas é atualmente o tratamento padrão quando o sangramento não responde a medidas locais e/ou a medicamentos antifibrinolíticos, podendo, entretanto, resultar em aloimunização. O fator VII recombinante ativado (rFVIIa) pode ser usado para evitar a transfusão recorrente de plaquetas. RELATO DE CASO: Apresentamos um tratamento precoce com dose baixa de rFVIIa associada à transfusão de plaquetas em um caso pediátrico (cinco anos de idade), com diagnóstico de TG e apresentando sangramento prolongado durante adenoidectomia eletiva. Uma dose total de 1.200 mg (60 µg.kg-1) de rFVIIa obteve sucesso em estancar o sangramento, o que pode ser aceito como uma dose baixa. CONCLUSÕES: Relatos de casos podem encorajar o uso de tratamento precoce com baixas doses de rFVIIa em hemorragias graves que não estacam a despeito da transfusão de plaquetas e na prevenção de sangramento em procedimentos cirúrgicos em pacientes com TG. Estudos adicionais são necessários para definir a dose mínima eficaz. Portanto, as tentativas para determinar a dose eficaz mais baixa desse composto devem ser incentivadas consideando o resultado deste caso em face de restrições financeiras no sistema de saúde.

BACKGROUND AND OBJECTIVE: Glanzmann's thrombasthenia (GT) is an autosomal recessively inherited platelet disorder. There is not any specific treatment. Platelet transfusion is currently the standard treatment when bleeding does not respond to local measures and/or antifibrinolytic treatment, although it may result in alloimmunization. Recombinant activated factor VII (rFVIIa) might be used to avoid recurrent platelet transfusion. CASE REPORT: We present early treatment with low-dose rFVIIa additional to platelet transfusion in a 5-year-old pediatric case with diagnosis of GT who developed prolonged bleeding under an elective adenoidectomy surgery. A total dose of 1,200 µg (60 µg.kg-1) rFVIIa could successfully stop bleeding, what can be accepted as low dose usage. CONCLUSIONS: Such case reports may encourage the use of early treatment with low doses of rFVIIa in severe bleeds that did not stop despite of platelet transfusion, as well as in preventing bleeding in surgical procedures in patients with GT. Actually, additional studies are needed to define the minimal effective dose and attempts to determine the lowest effective dose may be encouraged by the result of this case, considering financial restrictions in the health care system.

JUSTIFICATIVA Y OBJETIVOS: La Trombastenia de Glanzmann (TG) es una enfermedad autosómica recesivamente hereditaria de las plaquetas. No hay ningún tratamiento específico. La transfusión de plaquetas es hoy por hoy, el tratamiento estándar cuando el sangramiento no responde a medidas locales y/o a medicamentos antifibrinolíticos, pudiendo sin embargo, resultar en una aloinmunización. El factor VII recombinante activado (rFVIIa) puede ser usado para evitar la transfusión recurrente de plaquetas. RELATO DE CASO: Presentamos aquí un rápido tratamiento con una dosis baja de rFVIIa asociada a la transfusión de plaquetas en un caso pediátrico (5 años de edad), con diagnóstico de TG y presentando un sangramiento prolongado durante la adenoidectomía electiva. Una dosis total de 1.200 mg (60 µg.kg-1) de rFVIIa tuvo éxito al estancar el sangramiento, lo que puede aceptarse como una dosis baja. CONCLUSIONES: Relatos de casos pueden estimular el uso de tratamiento rápido con bajas dosis de rFVIIa en las hemorragias graves que no estancan, pese a la transfusión de plaquetas y a la prevención de sangramiento en los procedimientos quirúrgicos en pacientes con TG. Sin embargo, estudios adicionales se hacen necesarios para definir la dosis mínima eficaz. Por tanto, los intentos para determinar la dosis eficaz más baja de un compuesto tan caro deben ser incentivados debido al resultado de este caso cuando existan restricciones financieras en el sistema de Sanidad.

Perioperative management of a pediatric patient with Glanzmann's thrombasthenia during adenoidectomy.

BACKGROUND AND OBJECTIVE: Glanzmann's thrombasthenia (GT) is an autosomal recessively inherited platelet disorder. There is not any specific treatment. Platelet transfusion is currently the standard treatment when bleeding does not respond to local measures and/or antifibrinolytic treatment, although it may result in alloimmunization. Recombinant activated factor VII (rFVIIa) might be used to avoid recurrent platelet transfusion. CASE REPORT: We present early treatment with low-dose rFVIIa additional to platelet transfusion in a 5-year-old pediatric case with diagnosis of GT who developed prolonged bleeding under an elective adenoidectomy surgery. A total dose of 1,200µg (60µg.kg(-1)) rFVIIa could successfully stop bleeding, what can be accepted as low dose usage. CONCLUSIONS: Such case reports may encourage the use of early treatment with low doses of rFVIIa in severe bleeds that did not stop despite of platelet transfusion, as well as in preventing bleeding in surgical procedures in patients with GT. Actually, additional studies are needed to define the minimal effective dose and attempts to determine the lowest effective dose may be encouraged by the result of this case, considering financial restrictions in the health care system.

Binding of galectin-1 to αIIbß3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis.

Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a ß-galactoside-binding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry analysis, as well as studies using blocking antibodies against the anti-α(IIb) subunit ofα(IIb)ß(3) integrin or platelets from patients with Glanzmann's thrombasthenia syndrome (α(IIb)ß(3) deficiency), identified this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to platelets triggered the phosphorylation of ß(3)-integrin, Syk, MAPKs, PI3K, PLCγ2, thromboxane (TXA(2)) release, and Ca(2+) mobilization. Not only soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient (Lgals1(-/-)) mice showed increased bleeding time (P<0.0002, knockout vs. wild type), which was not associated with an abnormal platelet count. Lgals1(-/-) platelets exhibited normal aggregation to PAR4, ADP, arachidonic acid, or collagen but abnormal ATP release at low collagen concentrations. Impaired spreading on fibrinogen and clot retraction with normal levels of α(IIb)ß(3) was also observed in Lgals1(-/-) platelets, indicating a failure in the "outside-in" signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation.

Utilidad clínica de la agregometría plaquetaria / Clinical utility of platelet aggregometry

Resumen: La acción de las plaquetas en la hemostasia primaria comprende la adhesión a losvasos sanguíneos afectados, la activación, la secreción del contenido granular, y posteriormente,la agregación plaquetaria para la formación del tapón hemostático primario. Bajo las condicionesfisiológicas de flujo vascular, estos procesos requieren la acción sinérgica de varias proteínasy receptores plaquetarios, como también de agonistas que inducen la activación plaquetaria.Por ello, las mutaciones de los genes que codifican para moléculas y receptores de superficieimplicados en estos procesos darán origen a desórdenes hemorrágicos como la enfermedad devon Willebrand, la trombastenia de Glanzmann, el síndrome de Bernard Soulier y la deficienciade gránulos plaquetarios, entre otros. El diagnóstico de estas enfermedades se realiza medianteensayos de función plaquetaria que simulan los procesos fisiológicos de activación, adhesión,liberación del contenido granular y agregación. Una de las pruebas de función plaquetaria másutilizada es la agregometría. En este artículo de revisión se describe la utilidad de esta prueba parael diagnóstico de desórdenes hemorrágicos hereditarios y del síndrome de la plaqueta pegajosa,un desorden trombótico hereditario caracterizado por hiperagregabilidad. Adicionalmente, se revisa el fundamento de esta prueba, las condiciones preanalíticas, analíticas y posaanaliticas, analiticas y poanaliticas las indicaciones las contraindicaciones y la interpetación de los resultados.

Abstract: The role of platelets in primary hemostasis involves their adherence to sites of vessel injury, activation, secretion of platelet granule content, and finally, aggregation to form the primaryhemostatic plug. Under physiologic conditions of vascular flow, these processes require thesynergistic action of several proteins and platelet receptors, and also the action of physiologicalagonists that stimulate the activation of the platelets. As a result, hereditary mutations of genescodifying for molecules and surface receptors implied in primary hemostasis will be expressedas hemorrhagic disorders, including von Willebrand disease, Glanzmann thrombasthenia,Bernard Soulier syndrome, storage pool diseases, among others. The diagnosis of these diseases is possible through platelet function assays that resemble the physiological processesof activation, adhesion, release of granule content, and aggregation. Platelet aggregometry isone of the most frequently used tests. This review article intends to describe the utility of plateletaggregometry for the diagnosis of hereditary hemostatic disorders and sticky platelet syndrome, a hereditary thrombotic disorder characterized by increased platelet aggregability. In addition, the fundamentals of the test, the pre-analytical, analytical and post-analytical conditions, the test indications, contraindications and results interpretation are discussed.

Human platelets express and are activated by galectin-8.

Gals (galectins) are proteins with glycan affinity that are emerging as mediators of atherosclerosis. Despite the similarities in structure and sequence, different Gals exert distinct effects on their target cells. We have shown that Gal-1 triggers platelet activation, suggesting a role for Gals in thrombus formation. Since Gal-8 is expressed upon endothelial activation and also contributes to inflammation, to understand further the role of these lectins in haemostasis, we evaluated the effect of Gal-8 on human platelets. Gal-8 bound specific glycans in the platelet membrane and triggered spreading, calcium mobilization and fibrinogen binding. It also promoted aggregation, thromboxane generation, P-selectin expression and granule secretion. GP (glycoprotein) αIIb and Ib-V were identified as putative Gal-8 counter-receptors by MS. Studies performed using platelets from Glanzmann's thromboasthenia and Bernard-Soulier syndrome patients confirmed that GPIb is essential for transducing Gal-8 signalling. Accordingly, Src, PLC2γ (phospholipase C2γ), ERK (extracellular-signal-regulated kinase) and PI3K (phosphoinositide 3-kinase)/Akt downstream molecules were involved in the Gal-8 signalling pathway. Gal-8 fragments containing either the N- or C-terminal carbohydrate-recognition domains showed that activation is exerted through the N-terminus. Western blotting and cytometry showed that platelets not only contain Gal-8, but also expose Gal-8 after thrombin activation. These findings reveal Gal-8 as a potent platelet activator, supporting a role for this lectin in thrombosis and inflammation.

Trastornos plaquetarios primarios en la especie humana, aspectos biomédicos: biología, patobiología y bioclínica / Primary platelet disorders in humans, biomedical aspects: Biology, Pathobiology and bioclinical

Las enfermedades genéticas plaquetarias son desórdenes heterogéneos, algunos de ellos muy raros, quese presentan en la medicina clínica, caracterizados por trobocitopenia, plaquetas grandes (macrotrombocitopenias)y signos variables de hemorragia, así como trombosis en otros casos. La patogénesis ypatofisiología es bastante desconocida y el propósito de este artículo es proveer una estructura lógicaque resuma el conocimiento actual.

Enfermedad de Glanzmann: un desafío terapéutico en cirugía y periodoncia. Análisis de una situación clínica / Glanzmman disease: a therapeutic challenge in surgery and periodontics. Analysis of a clinical situation

Los odontólogos somos, dentro del equipo de salud, profesionales que tenemos posibilidades de ver a gran cantidad de pacientes y a éstos, muchas veces, a lo largo de su vida. Por tal motivo, podremos atender personas con trastornos sistémicos diagnosticados o no, como puede ser el caso de los trastornos en la coagulación. En la siguiente revisión se mencionarán los principales signos y síntomas gingivo-periodontales de estas patologías y las consideraciones básicas para el manejo local de las hemorragias espontáneas o postratamiento. El caso que se presenta es respecto a una tromboastenia de Glanzmann, cuya característica es el sangrado gingival espontáneo, pero no tanto a nivel quirúrgico

Enfermedad de Glanzmann: un desafío terapéutico en cirugía y periodoncia. Análisis de una situación clínica / Glanzmman disease: a therapeutic challenge in surgery and periodontics. Analysis of a clinical situation

Los odontólogos somos, dentro del equipo de salud, profesionales que tenemos posibilidades de ver a gran cantidad de pacientes y a éstos, muchas veces, a lo largo de su vida. Por tal motivo, podremos atender personas con trastornos sistémicos diagnosticados o no, como puede ser el caso de los trastornos en la coagulación. En la siguiente revisión se mencionarán los principales signos y síntomas gingivo-periodontales de estas patologías y las consideraciones básicas para el manejo local de las hemorragias espontáneas o postratamiento. El caso que se presenta es respecto a una tromboastenia de Glanzmann, cuya característica es el sangrado gingival espontáneo, pero no tanto a nivel quirúrgico (AU)

Surgical and clinical management of a patient with Glanzmann thrombasthenia: a case report.

A 6-year-old girl with Glanzmann thrombasthenia presented with caries and periapical lesions in the primary mandibular second molars and moderate gingivitis of the maxillary and mandibular anterior teeth. Dental extraction was recommended, and before every surgical intervention, the patient underwent platelet-concentrate transfusion to prevent hemorrhage. Epsilon aminocaproic acid was administered 6 hours before, and 48 hours after every dental procedure to prevent bleeding. In this case, treatment was effective in the prevention of hemorrhagic complications, during the required dental procedures.