Neutropenia

Descrição Geral

Definição

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 é uma diminuição do número de neutrófilos circulantes no sangue, que é tipicamente definida como uma contagem absoluta de neutrófilos (CAN) de:

• < 5000 células/µL em adultos e crianças > 1 ano de idade:
  • 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 ligeira: 1000-1500 células/µL
  • 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 moderada: 500-1000 células/µL
  • 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: < 500 células/µL
  • Agranulocitose: < 100-200 células/µL
• < 1000 células/µL em crianças de 2 semanas a 1 ano de idade
• < 5000 células/µL em bebés durante os seus primeiros dias de vida

Neutrófilos

Os neutrófilos são os mais MAIS Androgen Insensitivity Syndrome comuns de todos os leucócitos. Os leucócitos são glóbulos brancos e são um componente importante do sistema imunológico.

• Os neutrófilos respondem rapidamente no local da infeção.
• Os neutrófilos são leucócitos granulocíticos:
  • Contêm enzimas, oxidantes e proteínas, dentro de 4 tipos de grânulos, todos formados durante a diferenciação dos neutrófilos:
    • Grânulos azurofílicos (primários): contêm proteínas antibacterianas como a mieloperoxidase e o CAP37; funcionam principalmente dentro dos fagolisossomas
    • Grânulos específicos: contêm proteínas antibacterianas, tais como lactoferrina, gelatina neutrofílica associada à lipocalina, catelicidina e lisozima e proteases Proteases Proteins and Peptides, tais como colagenase.
    • Grânulos de gelatinase: contêm proteína antibacteriana, lisozima e as proteases Proteases Proteins and Peptides gelatinase (matriz metaloproteinase 9) e leucolisina
    • Grânulos secretores: contêm receptores transmembrana (por exemplo, receptores de fator de necrose tumoral e receptores interferon-α) que se integram na membrana plasmática dos neutrófilos à medida que ocorre a exocitose.
  • Pode produzir armadilhas extracelulares de neutrófilos (neutrophil extracellular traps (NETs)):
    • Compostas por redes de microfibras extracelulares, compostas na sua maioria por ADN de neutrófilos disrompidos.
    • As redes ligam e degradam bactérias e outros agentes patogénicos.
• Outros termos:
  • Frequentemente referidos como PMNs (polimorfonucleares)
  • Neutrófilos mais jovens e imaturos conhecidos como “bandas” ou “stab cells”
• Tipicamente reportado num hemograma completo como uma percentagem da contagem de leucócitos
• Contagem absoluta de neutrófilos (CAN):
  • O número de neutrófilos (em oposição à percentagem de leucócitos) que circulam por µL de sangue
  • CAN = glóbulos brancos/µL × percentagem (neutrófilos segmentados + bandas)
  • Exemplo:
    • Glóbulos brancos = 5600 células/µL; neutrófilos = 5%; bandas = 2%
    • Contagem absoluta de neutrófilos = 5600 × 7% = 392 células/µL
• Níveis normais de CAN (contagem absoluta de neutrófilos): variam de acordo com a idade

Significado clínico da 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

• A correlação entre a CAN e o risco infeccioso aplica-se apenas às condições em que a reserva de neutrófilos da medula óssea está diminuída, como a toxicidade hematológica da quimioterapia.
• Com 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 ligeira não relacionada com a terapia (CAN, 1000-1500 células/µL), não há um risco significativamente aumentado de infeção.
• Com 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 (CAN, < 500/µL), há um risco significativo de infeção; a febre deve ser tratada em regime de internamento com antibióticos parenterais, mesmo com poucos sinais clínicos de infeção.

Epidemiologia

Prevalência:

• 1%–10% em indivíduos saudáveis e assintomáticos
• Maior naqueles com determinadas condições médicas:
  • Doenças auto-imunes: lúpus eritematoso sistêmico (LES), artrite reumatóide
  • Doenças do tecido conjuntivo
• Varia por etnia:
  • Negros: 4.5%–10.5%
  • Brancos: 0.79%
  • Mexicano-americanos: 0.38%

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 pode ocorrer como uma característica isolada ou em associação com outras anomalias hematológicas e/ou defeitos da medula óssea (por exemplo, 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 megaloblástica ou leucemia).

Fisiopatologia

Revisão da fisiologia normal

Os neutrófilos maduros são produzidos por precursores na medula óssea.
Os neutrófilos podem ser encontrados em três compartimentos:

• Medula óssea; aqui os neutrófilos podem ser classificados como:
  • Proliferativos: em desenvolvimento
  • Armazenados: neutrófilos maduros
• Sangue: aqui os neutrófilos podem ser classificados como:
  • Circulantes
  • Marginados: aderentes ao endotélio vascular ou localizados dentro do baço
• Tecidos: Os neutrófilos deixam o sangue ao acaso após cerca de 6-10 horas para entrar nos tecidos, onde atuam para destruir patogénios ou sofrer apoptose.

Mecanismos que levam à 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

• Diminuição da produção/diferenciação na medula óssea:
  • Precursores hematopoiéticos danificados (por exemplo, quimioterapia, radiação, infeção)
  • Granulopoiese ineficaz (por exemplo, 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 megaloblástica)
  • Infiltração da medula óssea (por exemplo, leucemia)
• Marginação:
  • Mudança dos PMNs circulantes para o endotélio vascular ou baço
  • Exemplo: endotoxina pode causar marginação → ↓ neutrófilos circulantes (às vezes chamados de pseudoneutropenia)
• Aumento da destruição imunitária à periferia:
  • Reações a medicamentos
  • Processo auto-imune

Etiologia

A neutropenia é mais comumente adquirida, frequentemente após infeções ou como um efeito colateral de uma série de diferentes medicamentos. Raramente, a neutropenia pode ser “primária” ou congénita como parte de uma síndrome menos comum.

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 adquirida: não-induzida por drogas

• Infeções (forma mais MAIS Androgen Insensitivity Syndrome comum 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 adquirida):
  • Virais, incluindo:
    • CMV
    • Vírus Epstein-Barr
    • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza
    • Hepatite vírica
    • VIH
  • Bactérias, incluindo:
    • Sépsis bacteriana
    • Tuberculose
    • Rickettsioses
  • Parasitárias:
    • Toxoplasmose
    • Malária
• Doenças malignas hematológicas (tipicamente presentes com pancitopenias):
  • Leucemias
  • Outras doenças linfoproliferativas
  • Síndrome mielodisplásica
  • Mielofibrose
• Supressão da medula óssea:
  • 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 aplástica
  • Radiação ionizante
  • Infiltração maligna
  • Medicamentos (ver abaixo)
• Hiperesplenismo
• Causas nutricionais:
  • Défice de vitamina B₁₂ ou folato ( 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 megaloblástica; pode ser vista no alcoolismo)
  • Défice de cobre
• Processo auto-imune e/ou associado a distúrbios reumatológicos:
  • Lupús eritematoso sistémico (LES)
  • Artrite reumatóide
  • Síndrome de Sjögren
  • Doença de Crohn
  • Granulomatose com poliangiite
  • Reações transfusionais
• Ativação do complemento:
  • Hemodiálise usando membranas não-biocompatíveis
  • Síndrome de dificuldade respiratória aguda
• 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 idiopática crónica

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 adquirida: induzida por fármacos

Alguns medicamentos, incluindo muitos agentes de quimioterapia, produzem previsivelmente mielossupressão dose-dependente. Muitos outros medicamentos estão associados 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 grave isolada (conhecida como reações medicamentosas idiossincráticas), ocorrendo tipicamente dentro de 3 meses após o início da medicação.

Medicamentos associados à mielossupressão (lista parcial, inclui muitos agentes quimioterápicos e imunossupressores):

• Metotrexato
• Ciclofosfamida
• Cisplatina, carboplatina
• Etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors
• Doxorrubicina
• Colchicina
• Azatioprina
• Ganciclovir Ganciclovir An acyclovir analog that is a potent inhibitor of the herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from aids-associated cytomegalovirus infections. Antivirals for Herpes Virus

Medicamentos associados à 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 associada a reações medicamentosas idiossincráticas (lista parcial, os mais MAIS Androgen Insensitivity Syndrome comuns estão em negrito):

• Antibióticos: Penicilinas (especialmente penicilina G), cefalosporinas, sulfonamidas, macrolídos, vancomicina, dapsona
• Antimaláricos: cloroquina, quinino
• Antifúngicos: anfotericina B, flucitosina
• Antivíricos: aciclovir, oseltamivir Oseltamivir An acetamido cyclohexene that is a structural homolog of sialic acid and inhibits neuraminidase. Antivirals for Influenza, ganciclovir Ganciclovir An acyclovir analog that is a potent inhibitor of the herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from aids-associated cytomegalovirus infections. Antivirals for Herpes Virus
• Anti-inflamatórios: AINEs, sulfasalazina, penicilamina
• Tionamidas (medicamentos para a tiróide): metimazol, propiltiouracil ( PTU PTU A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs)
• Drogas cardiovasculares: ticlopidina, procainamida, propranolol Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for myocardial infarction; arrhythmia; angina pectoris; hypertension; hyperthyroidism; migraine; pheochromocytoma; and anxiety but adverse effects instigate replacement by newer drugs. Antiadrenergic Drugs, digoxina, inibidores da ECA, hidralazina
• Diuréticos: tiazidas, acetazolamida, espironolactona
• Psicotrópicos: clozapina, fenotiazinas, antidepressivos tricíclicos
• Antiepilépticos: fenitoína, carbamazepina, ácido valpróico
• Agentes anticancerígenos não mielo-supressores: rituximab Rituximab A murine-derived monoclonal antibody and antineoplastic agent that binds specifically to the cd20 antigen and is used in the treatment of leukemia; lymphoma and rheumatoid arthritis. Immunosuppressants, inibidores da tirosina quinase

Neutropenias congénitas ou primárias

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 está associada a múltiplas síndromes raras. Exemplos incluem:

• 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 familiar (étnica) benigna
• 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 hereditária (ou congénita)
• Síndrome de Kostmann
• 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 cíclica
• Síndrome de Shwachman-Diamond

Apresentação Clínica

Os pacientes com 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 ou serão assintomáticos, ou apresentar-se-ão com infeções ou com sintomas associados à causa subjacente da sua 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.

Infeções

Os sintomas principais relacionados diretamente com 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 envolvem infeções. As infeções virais podem causar 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, enquanto os pacientes com 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 moderada a grave são mais MAIS Androgen Insensitivity Syndrome propensos a desenvolver uma infeção bacteriana ou fúngica. Os pacientes com 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 podem apresentar-se com:

• Infeções recorrentes (por exemplo, otite média recorrente)
• Infeções oportunísticas (por exemplo, candidíase)
• Infeções graves com 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 (CAN < 200 células/µL):
  • Sépsis
  • Infeções gastrointestinais e pulmonares que ameaçam a vida

A maioria dos organismos comuns que causam infeções recorrentes, oportunistas e/ou graves:

• Bacilos Gram-negativos:
  • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
  • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella spp.
  • Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas
• Cocos Gram-positivos (especialmente em pacientes com cateteres instalados):
  • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus spp.
  • Streptococcus viridans Streptococcus viridans A large heterogeneous group of mostly alpha-hemolytic streptococci. They colonize the respiratory tract at birth and generally have a low degree of pathogenicity. This group of species includes Streptococcus mitis; Streptococcus mutans; Streptococcus oralis; Streptococcus sanguis; Streptococcus sobrinus; and the Streptococcus milleri group. The latter are often beta-hemolytic and commonly produce invasive pyogenic infections including brain and abdominal abscesses. Brain Abscess
• Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis spp., especialmente após pacientes neutropénicos receberem tratamento com antibióticos de amplo espectro

Os achados clínicos dependerão da localização da infeção e do organismo causador e frequentemente incluem:

• Febre
• Fadiga
• Linfadenopatia
• Achados na pele:
  • Exantema ( rash Rash Rocky Mountain Spotted Fever)
  • Celulite, úlceras e/ou abcessos
  • Icterícia (pode sugerir doença hepática secundária à hepatite viral)
• Achados do foro otorrinolaringológico:
  • Úlceras recorrentes na boca
  • Gengivite
• Achados pulmonares (se estiver presente uma pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia):
  • Tosse
  • Dispneia
  • Macicez à percussão
• Achados musculoesqueléticos:
  • Dor e/ou 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 nas articulações
  • Mialgias

Nota: Os pacientes não correm risco acrescido de infeções virais ou parasitárias, uma vez que estas infeções não são neutralizadas por neutrófilos.

Outras achados de história e exame físico

• Pode ser assintomática
• Histórico de medicamentos que podem causar 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
• Sintomas relacionados com a causa primária, por exemplo:
  • Lúpus eritematosos sistémico (LES)
    • Dor ou tumefação de articulações
    • Exantema ( rash Rash Rocky Mountain Spotted Fever)
    • Hematúria
    • Dor pleurítica
  • Mielofibrose:
    • Dor óssea
    • Fadiga e dispneia devido 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 concomitante

Diagnóstico

Avaliação analítica/laboratorial

• Hemograma completo com contagem diferencial:
  • Determina a severidade da 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
  • Determina se 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 é isolada ou associada a outras anomalias hematológicas (ajuda a estreitar o diagnóstico diferencial); por exemplo:
    • Eosinofilia → reações a medicamentos/alergias ou infeções parasitárias
    • Linfocitose → leucemias, linfomas
    • Linfopénia → imunodeficiência
    • 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 megaloblástica → défice de folato ou vitamina B₁₂
• Esfregaço de sangue:
  • Confirmar o número reduzido de neutrófilos
  • Neutrófilos hiper-segmentados → défice de folato ou vitamina B₁₂
  • Linfócitos atípicos → causa viral
  • Alterações consistentes com leucemias (por exemplo, linfócitos “smudge”, projeções capilares (hair-like), ou grânulos azurofílicos)
• Velocidade de sedimentação de eritrócitos (VS) e PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR): visto que os achados clássicos de infeção ou inflamação podem ser inaparentes
• Outros testes Testes Gonadal Hormones laboratoriais a considerar com base na história e nos achados:
  • Culturas de sangue e urina se febril
  • Teste de fezes se o paciente tiver diarreia infecciosa
  • Testes Testes Gonadal Hormones para causas reumatológicas:
    • Anticorpos antinucleares
    • Anticorpos Anti-DNA
    • Níveis de complemento
  • Rastreio para défices nutricionais:
    • Cobre sérico
    • Níveis de folato e vitamina B₁₂
  • Rastreio para infeção pelo VIH
  • Testes Testes Gonadal Hormones genéticos em caso de suspeita de síndromes congénitas

Outros testes Testes Gonadal Hormones

Outros testes Testes Gonadal Hormones a considerar com base na apresentação clínica incluem:

• Radiografia do tórax para avaliação de infeção ou doença maligna
• Ultrassonografia ou TC de abdómen para imagens de fígado e baço
• Aspiração e biópsia da medula óssea em caso de suspeita de doença maligna

Tratamento

Abordagem geral

O tratamento depende da causa e do grau da 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 .

• Descontinuar agentes farmacológicos causadores
• Repleção de défices vitamínicos causadores (vitamina B12, folato e/ou cobre).
• Monitore a CAN em hemogramas seriados:
  • Para a maioria dos pacientes, 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 será devida a uma infeção ou medicação.
  • Repetir o hemograma completo para assegurar a resolução da 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 após a melhoria da infeção/descontinuação dos agentes causadores.
  • Se 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 persistir, está indicada investigação adicional.
• Infeções:
  • Tratar as infeções com agentes apropriados.
  • Profilaxia contra infeção:
    • Lavagem das mãos para prevenir infeções
    • Evite a exposição a pessoas doentes.
    • Cuidados dentários regulares
• Nneutropenia associada à autoimunidade: Considere imunoglobulina IV ( IVIG IVIG Dermatomyositis) e/ou esteroides se 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 for grave e causada pela condição autoimune.
• Fatores estimulantes de colónias granulocíticas (G-CSFs):
  • Estimula naturalmente a produção de neutrófilos
  • Exemplos: filgrastim Filgrastim A recombinant granulocyte colony-stimulating factor (G-CSF) that is used in the treatment and prevention of neutropenia, preparation and collection of blood progenitor cells, and for use in peripheral blood stem cell transplantation. Hematopoietic Growth Factors, pegfilgrastim Pegfilgrastim Hematopoietic Growth Factors
  • Indicado em:
    • 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 febril aguda
    • Uso profilático em pacientes de quimioterapia em risco 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
    • Crianças com 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 congénita grave e/ou falência da medula óssea
    • 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 cíclica se a CAN < 200 e no caso de infeções estarem presentes
• Transplante de medula óssea: pode ser curativo para crianças com síndrome de Kostmann
• Indicações para referenciação hematológica imediata:
  • Blastos ou outros achados que sugiram doença maligna hematológica vistos em esfregaço de sangue periférico
  • CAN < 200
  • Pancitopenia

Tratamento da 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 febril em pacientes com cancro

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 febril é a complicação com risco de vida mais MAIS Androgen Insensitivity Syndrome comum dos tratamentos oncológicos.

• A antibioticoterapia empírica na apresentação é imperativa para melhorar os resultados e diminuir a mortalidade.
• Um organismo causador é identificado em apenas ⅓ dos casos e, portanto, os antibióticos devem visar o tratamento de um amplo espectro de patogénios esperados.
• Os antibióticos profiláticos e o tratamento com fator de crescimento no início da 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 demonstraram beneficiar apenas um pequeno subgrupo de pacientes de alto risco com cancro e a receber quimioterapia.

Diagnóstico Diferencial das Neutropenias Primárias

• 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 familiar (étnica) benigna: causa herdada 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 ligeira a moderada, mais MAIS Androgen Insensitivity Syndrome frequentemente observada em indivíduos de ascendência africana. Estes pacientes podem não gerar leucocitose durante a infeção, todavia a sua apresentação é normal. Eles geram febre e taquicardia durante a infeção (semelhante aos controlos), não têm uma incidência maior de infeção e não têm um risco aumentado 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 febril secundária à terapia mielossupressora. As reservas de medula óssea destes pacientes são normais.
• 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 hereditária / 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 congénita: condição resultante de mutações em 1 de vários 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, tipicamente herdada de forma autossómica dominante e muitas vezes levando 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 grave. Esta patologia é mais MAIS Androgen Insensitivity Syndrome comum em bebés e crianças pequenas. Os sintomas incluem feridas na boca, febre frequente, pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, infeções de ouvido e feridas retais. Se não for tratada imediatamente, uma criança pode começar a perder dentes como resultado de infeções gengivais graves.
• Síndrome de Kostmann: causa hereditária 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 congénita grave (CAN é frequentemente < 200). É herdada num padrão autossómico recessivo, embora os 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 causadores sejam desconhecidos. A síndrome de Kostmann é uma condição agressiva em que os pacientes são incapazes de produzir neutrófilos de forma eficaz. Os pacientes normalmente ficam muito doentes e podem necessitar de transplante de medula óssea, que é curativo.
• 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 cíclica: causa autossómica dominante 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 episódica, tanto em crianças como em adultos. Os episódios ocorrem aproximadamente a cada 3 semanas (intervalo, 12-35 dias) e continuam durante 3-6 dias num único ciclo. Os sintomas incluem febre, infeções e úlceras. Muitas crianças melhoram depois da puberdade.
• Síndrome de Shwachman-Diamond: síndrome muito rara que se apresenta na infância, herdada através dum padrão autossómico recessivo. A síndrome caracteriza-se por insuficiência pancreática, disostose metafisária (flaring nas extremidades dos ossos longos com constrição e esclerose da diáfise), atraso do crescimento e 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, com ou sem 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 ou trombocitopenia.