Hemoglobinuria Paroxística Nocturna

Descripción General

Epidemiología

• Prevalencia: aproximadamente 5 casos por cada millón de pacientes
• Razón con relación al AL Amyloidosis sexo: hombres = mujeres
• Edades afectadas: principalmente adultos jóvenes; también niños y personas de > 70 años

Etiología

• Mutación somática ligada al AL Amyloidosis cromosoma X, del gen de la subunidad A de la fosfatidilinositol N-acetilglucosaminiltransferasa (PIG-A) 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 una célula madre hematopoyética multipotente
• Gen PIG-A: responsable del 1er paso 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 síntesis del glucosilfosfatidilinositol
• El glucosilfosfatidilinositol ancla decenas de proteínas a la superficie celular, incluidos los LOS Neisseria inhibidores del complemento (reguladores) CD59 y CD55.
• CD59: protege los LOS Neisseria eritrocitos contra la hemólisis intravascular mediada por el complejo de ataque a membrana
• CD55: protege los LOS Neisseria eritrocitos contra la opsonización por el complemento C3b y la posterior hemólisis extravascular
• Los LOS Neisseria eritrocitos pueden mostrar una ausencia parcial o total de proteínas ancladas a glucosilfosfatidilinositol.
• La expansión clonal benigna de las células madre mutadas da lugar a eritrocitos deficientes 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 CD59/CD55.

Clasificación

Hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions paroxística nocturna (HPN) clásica:

• Evidencia clínica de hemólisis intravascular:
  • Reticulocitosis
  • ↑ LDH LDH Osteosarcoma sérica
  • ↑ Bilirrubina indirecta
  • Haptoglobina sérica baja
• No hay evidencia de una anormalidad preexistente definida de la médula ósea

HPN 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 marco de un trastorno específico de la médula ósea:

• Pruebas clínicas y de laboratorio de hemólisis
• Anomalía medular comórbida preexistente (o antecedente de una):
  • 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 aplásica
  • Síndrome mielodisplásico
  • Mielofibrosis

HPN subclínica:

• Anomalía medular comórbida preexistente (o antecedente de una):
  • 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 aplásica
  • Síndrome mielodisplásico
  • Mielofibrosis
• Pequeñas poblaciones de eritrocitos y/o granulocitos deficientes 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 proteínas ancladas a glucosilfosfatidilinositol, detectadas por análisis de citometría de flujo
• No hay evidencia clínica o por laboratorios de hemólisis

Fisiopatología

Genética

Gen PIG-A (fisiología normal):

• Situado 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 cromosoma X
• Codifica para glucosilfosfatidilinositol:
  • Ancla ciertas proteínas a la membrana celular
  • Ancla CD55 y CD 59 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 múltiples líneas de células sanguíneas:
    • Eritrocitos
    • Neutrófilos
    • Monocitos
    • Plaquetas
  • CD55 y CD59 son proteínas de superficie reguladoras del complemento:
    • Evitan la unión del complemento a las células sanguíneas circulantes
    • CD59 (también llamado inhibidor de membrana de la lisis reactiva) impide la formación del complejo de ataque a la membrana (evita la hemólisis intravascular).
    • CD55 (también llamado factor acelerador de la descomposición) impide la destrucción de las células sanguíneas mediada por la opsonización/complemento 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 bazo (evita la hemólisis extravascular).

Gen PIG-A (mutación):

• Mutación de las células progenitoras hematopoyéticas
• Produce la expansión clonal de múltiples líneas de células sanguíneas:
  • Eritrocitos
  • Neutrófilos
  • Monocitos
  • Plaquetas
• Las células sanguíneas carecen de las proteínas de superficie CD55 y CD59:
  • Amplificación incontrolada del sistema del complemento
  • Se produce hemólisis intravascular y extravascular.
  • Múltiples manifestaciones patológicas subsiguientes

Insuficiencia de la médula ósea

• Caracterizada por citopenias periféricas asociadas a hematopoyesis deficiente
• Presente, 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 cierto grado, 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 todos los LOS Neisseria pacientes con HPN
• Se desconoce el mecanismo de asociación entre la HPN y 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 aplásica:
  • 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 aplásica se desarrolla 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 10%–20% de los LOS Neisseria pacientes con HPN.
  • La hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions paroxística nocturna se desarrolla 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 5% de los LOS Neisseria pacientes con 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 aplásica.
• La insuficiencia de la médula ósea 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 HPN es muy variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables:
  • Disminución leve de las células madre hematopoyéticas (extremo leve del espectro)
  • 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 aplásica grave (extremo grave del espectro)
• Mecanismo de insuficiencia de la médula ósea 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 HPN:
  • El mecanismo propuesto es la destrucción de las células precursoras hematopoyéticas mediada por el complemento.
  • Todavía no se comprende completamente

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

• El mecanismo principal es la hemólisis intravascular:
  • Los LOS Neisseria eritrocitos circulantes carecen del efecto protector de CD59
  • Los LOS Neisseria factores del complemento ensamblan/activan el complejo de ataque a la membrana 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 membrana del eritrocito y provocan su lisis:
    • Hemoglobina liberada a la circulación
    • Múltiples manifestaciones patológicas subsiguientes
• El mecanismo secundario es la hemólisis extravascular:
  • Los LOS Neisseria eritrocitos circulantes carecen del efecto protector de CD55.
  • El complemento opsoniza o se acumula 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 membrana de los LOS Neisseria eritrocitos.
  • La opsonización marca los LOS Neisseria eritrocitos para su eliminación fagocítica 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 bazo.
• Otros factores que contribuyen 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:
  • Pérdida de hierro por lisis excesiva y crónica de los LOS Neisseria eritrocitos:
    • Algunas pérdidas de hierro por hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions
    • Parte del hierro se pierde por depósito 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 tejidos
  • Carencia de producción de eritrocitos:
    • Insuficiencia subyacente de la médula ósea
    • Deficiencia de hierro

Participación de los LOS Neisseria neutrófilos

Los LOS Neisseria neutrófilos también presentan una deficiencia de proteínas ancladas a glucosilfosfatidilinositol:

• Mayor sensibilidad a la lisis mediada por el complemento
• Una vez realizada la lisis, puede liberar citoquinas 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 circulación:
  • Aceleran aún más la actividad del complemento
  • Aumento del potencial trombogénico
• La lisis excesiva de neutrófilos puede conducir a una mayor susceptibilidad a infecciones.

Participación de las plaquetas

Los LOS Neisseria factores mediados por plaquetas incluyen:

• El déficit de óxido nítrico (NO) provoca activación y agregación de las plaquetas.
• Las plaquetas deficientes 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 proteínas ancladas a glucosilfosfatidilinositol se activan con el complemento.
• La falta de CD59 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 membranas de las plaquetas induce especialmente la agregación plaquetaria.

Trombofilia y trombosis

La trombosis 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 sitios inusuales (venas hepáticas, mesentéricas, cerebrales, cutáneas) es típica de la HPN.

• Factores mediados por NO:
  • 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 lisis de los LOS Neisseria eritrocitos, se libera hemoglobina 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 circulación
  • La hemoglobina se une a la haptoglobina hasta que esta se satura.
  • Tras saturar la haptoglobina, la hemoglobina libre se une al AL Amyloidosis NO circulante, que:
    • Normalmente, disminuye la adhesión endotelial
    • Normalmente, previene la activación y agregación de las plaquetas
    • Normalmente, causa vasodilatación
  • Pero si él NO se agota 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 circulación periférica:
    • ↓ NO aumenta la adhesión endotelial.
    • ↓ NO aumenta la activación y la agregación de las plaquetas.
    • ↓ NO provoca vasoconstricción → exposición del factor tisular → desencadena la cascada de coagulación extrínseca.
• Factores mediados por plaquetas:
  • La deficiencia de NO conduce a la activación y agregación de las plaquetas.
  • Las plaquetas deficientes 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 proteínas ancladas a glucosilfosfatidilinositol se activan con el complemento.
  • La falta de CD59 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 membranas de las plaquetas induce su agregación.
• Factores vasculares:
  • Activación del complemento 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 superficie de células endoteliales
  • La hemólisis intravascular puede proporcionar superficies de membrana friables 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 que puede iniciarse la coagulación.
  • Flujo lento: La trombosis de la HPN es mucho más frecuente 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 sistema venoso que 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 arterial, sobre todo 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 venas grandes o donde el flujo es más lento.
    • Hepático
    • Portal
    • Esplénica
    • Mesentérica
    • Pulmonar
    • Cerebrales
    • Cutáneas
• Otros factores:
  • Mecanismo desconocido de aumento de la actividad procoagulante y fibrinolítica
  • La lisis de los LOS Neisseria leucocitos puede liberar moléculas vasoactivas y/o trombogénicas.

Afectación renal

La insuficiencia renal es progresiva y multifactorial.

• Necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage tubular aguda como efecto del hemo y del hierro (nefropatía pigmentaria)
• Obstrucción tubular con cilindros pigmentados
• Disminución de la perfusión renal por trombosis de la vena renal
• Disminución de la perfusión renal por trombosis arterial
• Disminución de la perfusión renal por ↓ vasoconstricción mediada por NO

Distonía del músculo liso

• Tras la lisis de los LOS Neisseria eritrocitos, la hemoglobina se libera 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 circulación
• La hemoglobina se une a la haptoglobina hasta que esta se satura.
• Tras saturar la haptoglobina, la hemoglobina libre se une al AL Amyloidosis NO circulante, que:
  • Normalmente, relaja el tono del músculo liso
  • Su nivel desciende 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 circulación periférica
• El descenso del NO conduce a contracción del músculo liso.
• Las manifestaciones clínicas dependen de la población de células de músculo liso afectada.

Paroxismos de hemólisis

Las exacerbaciones de la hemólisis pueden deberse a:

• Administración de hierro a un paciente con deficiencia de hierro:
  • Eritrocitos carentes de CD59/CD55 son liberados a la circulación
  • Se produce hemólisis intra/extravascular
• Activación exógena del sistema del complemento:
  • Infección/ sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
  • Cirugía/traumatismos
  • Medicamentos

Participación de los LOS Neisseria anticuerpos

• El test de Coombs detecta la presencia de anticuerpos 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 anemias hemolíticas autoinmunes.
• La HPN no tratada es una 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 hemolítica Coombs-negativa.
• La positividad de Coombs suele darse 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 pacientes con HPN tratadas con eculizumab:
  • Eculizumab es un anticuerpo monoclonal que bloquea la formación del complejo de ataque a la membrana mediada por el complemento:
    • No se produce hemólisis intravascular.
    • Este anticuerpo se detecta mediante el test de Coombs.
  • Los LOS Neisseria factores del complemento que no se consumen 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 formación del complejo de ataque a la membrana quedan libres 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 circulación y recubren las superficies de eritrocitos que carecen de la protección de CD55:
    • El eritrocito es ahora opsonizado por el complemento.
    • Los LOS Neisseria eritrocitos opsonizados sufren hemólisis extravascular.

Presentación Clínica

Síntomas asociados a hemólisis

• Hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions:
  • Clásicamente, se nota 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 1ra orina de la mañana
  • Puede ocurrir a cualquier hora del día o de la noche
  • De naturaleza intermitente (paroxística)
• Ictericia
• Nefrotoxicidad relacionada con el hemo/hierro:
  • Insuficiencia renal aguda
  • Enfermedad renal crónica

Síntomas asociados 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

• Fatiga
• Debilidad
• Disnea
• Palpitaciones
• Palidez
• Taquicardia

Síntomas asociados a contracción del músculo liso

Estos síntomas se deben a la disminución del NO circulante:

• Disfagia (esofágico)
• Náuseas (intestinal)
• Dolor Dolor Inflammation abdominal (intestinal)
• Disfunción eréctil (microvascular/cuerpo cavernoso)
• Hipertensión pulmonar (arteria pulmonar)

Síntomas asociados a trombosis

• Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema/cambio de coloración/ dolor Dolor Inflammation de las extremidades por trombosis venosa profunda (TVP)
• Embolia pulmonar
• La trombosis de las venas cerebrales/senos durales provoca:
  • Déficit neurológico focal
  • Hipertensión intracraneal
  • Encefalopatía
• La trombosis de la vena cutánea conduce a:
  • Equimosis
  • Púrpura fulminante
• La trombosis de la vena hepática/portal/mesentérica provoca:
  • Dolor Dolor Inflammation abdominal
  • Esplenomegalia
  • Síndrome de Budd-Chiari

Síntomas asociados a neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia

• Susceptibilidad a infecciones
• El aumento de las citoquinas circulantes conduce a:
  • Malestar/fatiga
  • Inflamación
  • Síndrome similar a la sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock

Diagnóstico

Hemograma

• 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 (↓ recuento de eritrocitos, ↓ hematocrito):
  • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables, pero generalmente presente 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 algún grado
  • Puede ser sutil o pronunciada dependiendo del grado de hemólisis
  • Puede o no ser normocítica, microcítica o macrocítica, dependiendo del grado de deficiencia de vitamina B₁₂, folato o hierro
• ↓ o normal recuento de neutrófilos
• ↓ o normal recuento de plaquetas
• ↑ Hemoglobina libre

Química

• ↑ AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests/ ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests (si hay congestión hepática)
• ↑ Creatinina (si hay toxicidad renal)
• ↑ Bilirrubina
• ↑ LDH LDH Osteosarcoma
• ↓ Fosfatasa alcalina leucocitaria

Análisis de orina

• Coloración roja o rosada macroscopica
• Hemoglobina positiva
• No hay eritrocitos 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 microscopía
• +/- proteínas 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 función de la integridad renal

Análisis de médula ósea

• El déficit de proteínas ancladas a glucosilfosfatidilinositol puede demostrarse 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 células de la médula ósea mediante citometría de flujo.
• Innecesario para el diagnóstico estándar de la HPN
• Necesario para una correcta clasificación:
  • Evaluar otros síndromes de insuficiencia medular.
  • Evaluar otras mielopatías clonales.

Citometría de flujo de sangre periférica

• Indicada para el tamizaje de:
  • Hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions
  • Hemólisis intravascular Coombs-negativa
  • LDH LDH Osteosarcoma sérica anormalmente alta, especialmente con déficit de hierro concomitante
  • Trombosis venosa 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 lugares no habituales
  • 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 aplásica ( 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 momento del diagnóstico y una vez al AL Amyloidosis año)
  • 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 refractaria
  • Síndrome mielodisplásico
  • Disfagia episódica o dolor Dolor Inflammation abdominal con evidencia de hemólisis intravascular
• Indicada para el diagnóstico definitivo y el seguimiento de la HPN:
  • Debe mostrar ≥ 5% de población de eritrocitos deficientes 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 CD55 y CD59 o ≥ 20% de granulocitos deficientes 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 CD55/CD59 para diagnosticar HPN.
  • Los LOS Neisseria pacientes con una deficiencia probada de proteínas ancladas a GPI deben ser monitoreados anualmente para dar seguimiento al AL Amyloidosis tamaño de la población clonal.

Tratamiento

Tratamiento médico

• Eculizumab o ravulizumab: anticuerpos monoclonales humanizados que se unen al AL Amyloidosis componente del complemento C5
• Previene la escisión de C5 y la hemólisis intravascular por complejos de ataque a la membrana
• Efecto:
  • Eliminación o notable reducción de las transfusiones de sangre
  • Disminución marcada de las complicaciones trombóticas
• Administración:
  • IV cada 2 semanas para eculizumab
  • IV cada 8 semanas para ravulizumab
• Desventajas:
  • Mayor riesgo de infecciones por Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria potencialmente mortales, que requieren vacunación previa al AL Amyloidosis tratamiento y antibióticos diarios para profilaxis
  • Costo elevado: aproximadamente 400 000 dólares (EE. UU.)/año
• La hemólisis extravascular continuará, debido a la opsonización de los LOS Neisseria eritrocitos por los LOS Neisseria fragmentos de C3.

Trasplante de médula ósea

• La única cura definitiva, pero tiene importantes riesgos intrínsecos
• Indicado sobre todo para:
  • 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 aplásica grave
  • Síndrome mielodisplásico severo
  • Complicaciones de la HPN que no responden a los LOS Neisseria inhibidores del complemento (o si no están disponibles)

Terapia de soporte

• Siempre se proporciona, independientemente de otras terapias ofrecidas
• Transfusiones de eritrocitos de sangre leucorreducida/filtrada (utilizada ahora de forma rutinaria para toda sangre transfundida):
  • Disminuye el riesgo de reacción de anticuerpos a los LOS Neisseria antígenos leucocitarios
  • Disminuye la activación del complemento
• Suplemento de vitamina B₁₂/ácido fólico si hay hemólisis 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 curso
• Suplemento de hierro si hay deficiencia de hierro debido a la hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions
• Anticoagulantes 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 pacientes con antecedentes o predisposición genética a la trombosis: anticoagulación de por vida si es de alto riesgo o si se ha HA Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia producido una trombosis atípica
• Monitoreo regular Regular Insulin (cada 6–12 meses):
  • Hemograma completo con diferencial
  • Recuento de reticulocitos
  • LDH LDH Osteosarcoma
  • Química sanguínea (electrolitos, función renal, función hepática)
  • Estudios del hierro (hierro sérico, capacidad total de fijación del hierro y ferritina)
  • Citometría de flujo para determinar cualquier cambio 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 tamaño del clon de HPN
  • Biopsia de médula ósea si hay pancitopenia o sospecha 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 aplásica o síndrome mielodisplásico

Pronóstico

• Historia natural, solo con medidas de soporte:
  • Mediana de supervivencia tras el diagnóstico: 10–20 años
  • Complicaciones principales:
    • Pancitopenia
    • Trombosis
    • Síndrome mielodisplásico
  • Causas de muerte:
    • Trombosis venosa: primera causa
    • Infección 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 caso de neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia grave
    • Leucemia mieloide aguda
• Con los LOS Neisseria inhibidores del complemento (eculizumab y ravulizumab), la mortalidad parece similar a la de los LOS Neisseria controles emparejados por edad, pero los LOS Neisseria datos temporales son limitados hasta ahora
• Trasplante de médula ósea: curativo pero con importantes riesgos inherentes
• Rara vez se produce una recuperación completa y espontánea.

Diagnóstico Diferencial

• 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 hemolítica: trastornos hereditarios (por ejemplo, deficiencia de glucosa-6-fosfato deshidrogenasa ( G6PD G6PD Pentose Phosphate Pathway), esferocitosis hereditaria, 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 células falciformes) o trastornos adquiridos (e.g., trastornos inmunitarios, productos químicos y medicamentos tóxicos, agentes antivirales, daños físicos, infecciones) que también se presentan con hemólisis que 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 (pero no con trombosis e insuficiencia de la médula ósea). Se trata de una categoría amplia, ya que cada una de las anemias hemolíticas tiene mecanismo, presentación y tratamiento únicos.
• 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 aplásica: se produce como resultado de un daño 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 células madre hematopoyéticas. Más del 10% de los LOS Neisseria casos 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 aplásica se convertirán 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 HPN. Además, algunas personas con HPN desarrollarán 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 aplásica. Al AL Amyloidosis igual que la HPN, 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 aplásica se presenta con insuficiencia de la médula ósea y recuento bajo de células sanguíneas (pero no con trombosis). El tratamiento de 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 aplásica puede incluir medicamentos, transfusiones de sangre o trasplante de células madre.
• Isquemia mesentérica aguda: se presenta con dolor Dolor Inflammation abdominal agudo 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 paciente con una fuente de trombos/embolias identificable, que obstruyen los LOS Neisseria vasos mesentéricos (e.g., ateroma preexistente, fibrilación auricular). Diagnosticado mediante angiografía. Tratada con embolectomía o cirugía para resecar el intestino necrótico.
• Hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions paroxística por frío: 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 hemolítica autoinmune rara que se observa 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 niños pequeños, desencadenada por una enfermedad infecciosa, una neoplasia o disfunción inmunitaria. Los LOS Neisseria anticuerpos IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions se unen a los LOS Neisseria eritrocitos 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 frío y fijan el complemento. Al AL Amyloidosis calentarse, los LOS Neisseria anticuerpos se disocian y el complemento realiza la lisis los LOS Neisseria eritrocitos, lo que provoca una hemólisis extravascular. El diagnóstico se realiza mediante test de Coombs. El tratamiento es preventivo.
• Obstrucción de la vena porta: suele estar causada por una trombosis primaria de la vena porta debida a una coagulopatía heredada, adquirida o asociada a cirrosis. También se produce obstrucción extrínseca. Los LOS Neisseria hallazgos clínicos suscitan la sospecha clínica, pero la presencia de una masa o un trombo 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 imagenología (ultrasonido o tomografía computarizada(TC)) es diagnóstica. El tratamiento incluye trombectomía, escisión de la masa/ tumor Tumor Inflammation, y/o anticoagulación.
• Trombosis de la vena renal: La causa más común de trombosis de la vena renal es el síndrome nefrótico. Otras causas son trastornos primarios de hipercoagulabilidad (como la HPN), tumores renales, compresión extrínseca, traumatismos y, raramente, enfermedad inflamatoria intestinal. Esta patología se presenta con insuficiencia renal (aguda o crónica). Diagnosticada con imágenes (ultrasonido o TC). El tratamiento incluye trombectomía, escisión de la masa/ tumor Tumor Inflammation, y/o anticoagulación.