Talasemia

Descripción General

Características de la enfermedad

• Las talasemias son trastornos hereditarios de la hemoglobina, de los LOS Neisseria genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure de la α o β-globina. Los LOS Neisseria defectos en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum estos genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure conducen a una estructura y función anormal de la hemoglobina y los LOS Neisseria eritrocitos.
• Se presenta como anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types hipocrómica microcítica:
  • Los LOS Neisseria casos leves pueden ser asintomáticos.
  • Los LOS Neisseria casos graves pueden dar lugar a esplenomegalia, hemólisis y anomalías óseas.

Epidemiología

• Prevalencia a nivel mundial:
  • α-Talasemia: 5%; más común en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum África y Asia ASIA Spinal Cord Injuries
  • β-Talasemia: 3%; más común en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el Mediterráneo
• Igual incidencia en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum hombres y mujeres

Etiología

• Trastorno autosómico recesivo
• α-Talasemia: 2 genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure α (HbA₁ y HbA₂) = 4 alelos (αα/αα)
  • Cromosoma 16: error Error Refers to any act of commission (doing something wrong) or omission (failing to do something right) that exposes patients to potentially hazardous situations. Disclosure of Information de supresión
  • 4 tipos de variaciones de la enfermedad:
    • Mínima: supresión de 1 α gen
    • Menor: supresión de 2 genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure α (mismo cromosoma = cis CIS Multiple Sclerosis, cromosomas opuestos = trans)
    • Enfermedad de hemoglobina H: supresión de 3 genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure α
    • Hemoglobina de Barts: supresión de 4 genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure α
• β-Talasemia: 1 gen β = 2 alelos
  • Cromosoma 11:
    • Mutación de empalme (β⁺: expresión disminuida) o
    • Mutación sin sentido (β⁰: ausencia de expresión)
  • 2 tipos de variaciones de la enfermedad:
    • Talasemia menor: heterocigoto, aproximadamente 50% de síntesis disminuida
    • Talasemia mayor: homocigoto, sin producción de β globulina, aumento de HbA₂(α₂δ₂) y HbF(α₂γ₂), sin HbA

Fisiopatología

• Formación defectuosa de la hemoglobina: conduce a la agregación de la hemoglobina, que daña las membranas de los LOS Neisseria eritrocitos
• Los LOS Neisseria eritrocitos dañados sufren hemólisis, lo que da lugar a:
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Cálculos biliares pigmentados
• La eritropoyesis ineficaz (debido a la falta de componentes normales de la hemoglobina) conduce a:
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types → insuficiencia cardíaca de alto gasto
  • Expansión de la médula ósea
  • Hematopoyesis extramedular → hepatomegalia y/o esplenomegalia
• Sobrecarga de hierro (por múltiples transfusiones para compensar los LOS Neisseria eritrocitos nativos dañados)
  • Aumento compensatorio de la captación gastrointestinal de hierro
  • Endocrinopatías

Presentación Clínica

Diagnóstico

Estudios iniciales

• Indagar antecedentes médicos y familiares (cribado en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum zonas de alto riesgo).
• Pedir hemograma con índices eritrocitarios y frotis de sangre periférica.
• En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el hemograma:
  • Hb Hb The oxygen-carrying proteins of erythrocytes. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Gas Exchange → generalmente < 11 g/dL o < 6 g/dL en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types de Cooley
  • VCM → microcítica (< 70 fL) en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum las talasemias
  • HCM HCM Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiomyopathy, which is characterized by an asymmetric increase in thickness (hypertrophy) of the left ventricular wall, diastolic dysfunction, and often left ventricular outflow tract obstruction. Hypertrophic Cardiomyopathy → baja en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum las talasemias
  • Ancho de distribución eritrocitaria → poco útil en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum las talasemias (puede ser normal o elevada)
• En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el frotis de sangre periférica:
  • Codocitos (más comunes)
  • Cuerpo de Howell-Jolly: mancha azul en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum los LOS Neisseria eritrocitos (restos de ADN)
  • Anisocitosis: Eritrocitos de tamaño desigual
  • Cuerpos de inclusión: se ven solo en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la enfermedad de la hemoglobina H (agregación 4 β)
  • Cuerpos de Heinz: mancha roja en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la periferia de los LOS Neisseria eritrocitos (hemoglobina desnaturalizada)
  • Punteado basófilo
  • Para recordar las características observadas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum un frotis de sangre periférica de un paciente con talasemia, recuerde la nemotecnia “THAL” ( en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum inglés):
    • T – Target cells (codocitos)
    • H – Howell-Jolly body (cuerpos de Howell Jolly)
    • A – Anisocytosis (anisocitosis)
    • L – Low MCH, MCV, and Hb Hb The oxygen-carrying proteins of erythrocytes. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Gas Exchange ( HCM HCM Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiomyopathy, which is characterized by an asymmetric increase in thickness (hypertrophy) of the left ventricular wall, diastolic dysfunction, and often left ventricular outflow tract obstruction. Hypertrophic Cardiomyopathy, VCM y Hb Hb The oxygen-carrying proteins of erythrocytes. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Gas Exchange descendidas)
• Si se sospecha hemólisis, pedir LDH LDH Osteosarcoma:
  • Si la LDH LDH Osteosarcoma está elevada y se sospecha hemólisis, pedir un recuento de reticulocitos: elevado en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la enfermedad de hemoglobina H.
• Pedir estudios de hierro: normales en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum las talasemias, anormales en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum otras causas de anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types

Estudios de confirmación

• Si los LOS Neisseria estudios de hierro son normales, pedir electroforesis de hemoglobina.
• Los LOS Neisseria estudios de electroforesis de hemoglobina normales muestran:
  • HbA: 95%
  • HbA₂: 3%–5%
  • HbF: cantidad mínima
  • Sin hemoglobina H o hemoglobina Barts, con electroforesis de hemoglobina normal
• En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la α-talasemia:
  • Mínima: porcentaje normal de HbA y HbA₂
  • Menor (rasgo): porcentaje normal de HbA y HbA₂, pero el hemograma muestra anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Enfermedad hemoglobina H: tétrada β (i.e., la electroforesis de hemoglobina mostrará solo una banda β)
  • Hemoglobina Barts: tétrada γ (i.e., la electroforesis de hemoglobina mostrará solo una banda γ)
• En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la β-talasemia
  • Menor:
    • ↓ HbA (93%)
    • ↑ HbA₂ (5%)
    • ↑ HbF (2%)
  • Mayor:
    • Sin HbA
    • ↑ HbF (90%)
    • ↑ HbA₂ (10%)
• Otros estudios auxiliares:
  • La radiografía mostrará una osteopenia Osteopenia Osteoporosis y un cráneo con aspecto de “pelos de punta”.
  • Un ecocardiograma puede mostrar una reducción de la fracción de eyección del ventrículo izquierdo.

Tratamiento

Talasemia menor α- y β-

• Los LOS Neisseria pacientes suelen ser asintomáticos y no está indicado ningún tratamiento crónico.
• La administración periódica de suplementos de folato puede ser útil durante estrés fisiológico (e.g., el embarazo).
• Proporcionar asesoramiento genético sobre el riesgo para la descendencia.

Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types de Cooley y enfermedad de hemoglobina H

• Transfusiones:
  • Los LOS Neisseria pacientes son dependientes de las transfusiones.
  • Nivel de Hb Hb The oxygen-carrying proteins of erythrocytes. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Gas Exchange objetivo > 10 g/dL
  • Suplemento de folato, si no hay transfusión
• Esplenectomía y colecistectomía:
  • Las esplenectomías reducen las necesidades de transfusión.
  • Vacunas postesplenectomía (organismos encapsulados)
    • Neumococo polivalente
    • Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus tipo b
    • Neumococo conjugada
  • Colecistectomía para prevenir los LOS Neisseria cálculos biliares recurrentes
• Quelación del hierro:
  • Reduce los LOS Neisseria niveles de hierro en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum suero
  • Deferoxamina (intravenoso)
  • Deferiprona/ deferasirox Deferasirox A triazole and benzoate derivative that acts as a selective iron chelator. It is used in the management of chronic iron overload due to blood transfusion or non-transfusion dependent thalassemia. Hereditary Hemochromatosis (formulaciones orales)
• Tratamiento endocrino:
  • Administrar hormonas deficientes.
  • Bifosfonatos para prevenir la osteopenia Osteopenia Osteoporosis y la osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
  • Agentes de fertilidad
• Tratamiento definitivo: trasplante de células madre alogénicas
• Asesoramiento genético

Diagnóstico Diferencial

El diagnóstico diferencial incluye otras afecciones asociadas a la anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types microcítica o a codocitos.

• Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types ferropénica: la otra causa principal de anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types hipocrómica microcítica, además de la talasemia. Los LOS Neisseria pacientes pueden presentar palidez y fatiga fácil. Se requieren estudios de hierro para obtener el diagnóstico. Los LOS Neisseria resultados del estudio del hierro indicarán una disminución de los LOS Neisseria niveles de hierro y un aumento de la capacidad total de fijación del hierro. El tratamiento es con suplementos de hierro por vía oral.
• Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types por enfermedad crónica (“ anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types de inflamación crónica”): secundaria a una enfermedad inflamatoria, infecciosa o maligna. Los LOS Neisseria pacientes presentan hallazgos similares a los LOS Neisseria de la deficiencia de hierro, es decir, palidez y fatiga fácil. Los LOS Neisseria estudios de hierro revelarán niveles bajos de hierro sérico y transferrina; sin embargo, los LOS Neisseria niveles de ferritina serán normales o estarán aumentados. El tratamiento está dirigido a resolver la enfermedad crónica subyacente.
• Enfermedad hepática: los LOS Neisseria codocitos pueden verse en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el frotis de sangre periférica de los LOS Neisseria pacientes con enfermedad hepática. Estos codocitos, que tienen un aspecto grande y en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum diana, se forman debido al AL Amyloidosis exceso de lípidos de la membrana.
• Pacientes postesplenectomía: los LOS Neisseria codocitos y los LOS Neisseria cuerpos de Howell-Jolly aparecen en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el frotis de sangre periférica de los LOS Neisseria pacientes después de una esplenectomía. Los LOS Neisseria pacientes también pueden presentar un aumento leve o marcado del recuento de plaquetas (trombocitosis).