Anemia aplásica adquirida

Question 1

Anemia aplásica

Answer 1

Distúrbio raro e heterogêneo definido como pancitopenia com meula óssea hipocelular na ausencia de infiltrados anormais ou fibrose de medula óssea.

Question 2

Qual a distribuição bifásica de idade na incidência de anemia aplásica?

Answer 2

São observados dois picos de incidência:
- Entre 10-25 anos de idade
- Mais de 60 anos de idade

Question 2

Definição de anemia aplásica grave (SAA)

Answer 2

• Celularidade medula óssea < 25% (ou 25-50% com < 30% de células hematopoiéticas residuais) mais pelo menos DUAS das seguintes:
• Neutrófilo < 500
• Plaquetas < 20.000
• Reticulócitos < 60.000

Question 3

Definição de anemia aplásica muito grave (VSAA)

Answer 3

• Celularidade medula óssea < 25% (ou 25-50% com < 30% de células hematopoiéticas residuais) mais pelo menos DUAS das seguintes:
• Neutrófilo < 200
• Plaquetas < 20.000
• Reticulócitos < 60.000

Mesmos critérios de anemia aplásica grave, mas com neutrólifos abaixo de 200

Question 4

Definição de anemia aplásica não grave

Answer 4

Não preencher os critérios para anemia aplásica grave ou muito grave

Question 5

Qual o nome dos critérios de gravidade de pacientes com anemia aplásica

Answer 5

Critérios de Camitta

Question 6

Qual a incidência de anemia aplásica na Europa e nos EUA?

Answer 6

Menos de 2 casos por 1.000.000 de pessoas por ano

Isso demonstra a raridade dessa doença na população.
Na Asia, no entanto, a incidência de AA é estimada em ser 2-3x maior. Isso sugere um potencial fator ambiental ou genético contribuindo para sua maior incidência.

Question 7

O que causa a perda de células progenitoras hematopoiéticas em pacientes com anemia aplásica?

Answer 7

Apoptose de células progenitoras causada por ataque imune mediado por linfócitos R e inibição de crescimento influenciado por citocinas inflamatórias

Question 8

What are hematopoietic stem cells (HSCs)?

Answer 8

Multipotent cells that give rise to all mature cells in peripheral blood and tissues

HSCs are essential for maintaining blood cell production.

Question 9

How can HSCs be recognized and isolated?

Answer 9

Based on their characteristic immunophenotype

HSCs are identified as part of the CD34-positive/CD38-negative fraction.

Question 10

What are the autoimmune mechanisms leading to the loss of HSCs in AA?

Answer 10

Pathogenic T cell responses and aberrant inflammatory cytokine production

These mechanisms contribute to the autoimmune nature of the disease.

Question 11

What therapies have shown the ability to cure some patients with AA?

Answer 11

T cell-directed therapies, such as antithymocyte globulin (ATG) and cyclosporine

These therapies highlight the autoimmune aspect of AA.

Question 12

What is hepatitis-associated AA (HAAA)?

Answer 12

Severe hepatitis followed by the onset of AA, usually within six months

HAAA has a distinct immune signature from idiopathic AA.

Question 13

What role do inflammatory cytokines play in AA?

Answer 13

They may suppress hematopoiesis in the bone marrow microenvironment

This suppression can lead to further complications in AA.

Question 14

What is a significant risk factor for the development of severe AA?

Answer 14

Prolonged exposure to solvents, industrial chemicals, insecticides, and pesticides

Benzene is particularly notorious among these risk factors.

Question 15

Which viral infections can cause marrow aplasia or hypoplasia?

Answer 15

Epstein-Barr virus (EBV), HIV, and seronegative hepatitis

These infections may trigger autoimmune responses leading to AA.

Question 16

What hematologic disorders may coexist with or evolve from AA?

Answer 16

Paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML)

Clonal evolution can complicate the clinical picture of AA.

Question 17

What are the most commonly mutated genes in adults with acquired AA?

Answer 17

DMNT3A, ASXL1, BCOR, BCORL1, and PIGA

These mutations are associated with AA and may also appear in clonal hematopoiesis.

Question 18

What is the most common karyotypic abnormality associated with AA?

Answer 18

Acquired uniparental disomy with loss of heterozygosity in the short arm of chromosome 6 (6pUPD)

This abnormality is linked to specific HLA class I allele losses.

Question 19

What are common clinical manifestations of AA?

Answer 19

Recurrent infections, mucosal hemorrhage, menorrhagia, and fatigue

These symptoms result from cytopenias associated with the disorder.

Question 20

What distinguishes inherited bone marrow failure syndromes (IBMFS) from AA?

Answer 20

IBMFS often presents with developmental delays and a family history of hematologic disorders

Identifying these features can help in differential diagnosis.

Question 21

What is the urgency of evaluation and bone marrow biopsy in suspected AA cases?

Answer 21

Guided by the depth of cytopenias and the patient’s clinical status

Critical cytopenias require immediate attention to prevent severe complications.

Question 22

What is the required examination to establish the diagnosis of AA?

Answer 22

A bone marrow examination is required to establish the diagnosis of AA.

AA stands for aplastic anemia.

Question 23

What factors guide the urgency of clinical evaluation and bone marrow biopsy in suspected AA?

Answer 23

The depth of cytopenias and the patient’s clinical status guide the urgency.

Cytopenias refer to reductions in the number of blood cells.

Question 24

What should be done for patients with critical cytopenias or life-threatening complications?

Answer 24

They should undergo immediate hematology consultation and hospitalization, including a bone marrow biopsy. ## Footnote Critical complications may include infections, bleeding, or cardiorespiratory compromise.

Question 25

What are the physical findings associated with pancytopenia in patients evaluated for AA?

Answer 25

Pallor and petechiae are common physical findings. ## Footnote Petechiae are small red or purple spots on the body caused by minor bleeding.

Question 26

What laboratory studies are important in evaluating pancytopenia?

Answer 26

Routine laboratory studies including complete blood count, blood smear, and serum chemistries provide clues to the cause. ## Footnote Serum chemistries can include kidney and liver function tests.

Question 27

What blood smear findings are typical in patients with AA?

Answer 27

Typically reveals normocytic red blood cells, but may show macrocytic or mildly microcytic red blood cells. ## Footnote Normocytic, macrocytic, and microcytic refer to the size of red blood cells.

Question 28

What are the characteristics of bone marrow findings in patients with AA?

Answer 28

Profound hypoplasia affects all hematologic elements; marrow space is mostly fat cells and stroma. ## Footnote Hypoplasia refers to underdevelopment or incomplete development of tissue or organs.

Question 29

What are the criteria for diagnosing severe AA (SAA)?

Answer 29

Cellularity <25% and peripheral blood showing ANC <500/microL, platelet count <20,000/microL, and reticulocyte count <60,000/microL. ## Footnote ANC stands for absolute neutrophil count.

Question 30

What is the distinction between very severe AA (vSAA) and severe AA (SAA)?

Answer 30

vSAA fulfills criteria for SAA with ANC <200/microL. ## Footnote ANC is a critical measure of immune function.

Question 31

What are potential reversible causes of cytopenias that must be distinguished from AA?

Answer 31

Reversible causes include cytotoxic chemotherapy effects, overwhelming sepsis, acute viral infection, and immunosuppressive agents. ## Footnote These causes can lead to transient cytopenia.

Question 32

What distinguishes megaloblastic anemia from AA?

Answer 32

Presence of hypersegmented neutrophils and macro-ovalocytes in blood smear and megaloblastic changes in bone marrow. ## Footnote Megaloblastic anemia is often due to vitamin B12 or folate deficiency.

Question 33

What is hypersplenism and how is it related to cytopenias?

Answer 33

Hypersplenism refers to cytopenias due to blood sequestration/redistribution to an enlarged spleen. ## Footnote Conditions like liver cirrhosis or portal vein thrombosis can cause hypersplenism.

Question 34

What are the malignancies associated with pancytopenia?

Answer 34

Myelodysplastic syndromes, acute myeloid leukemia, lymphoid leukemias, and lymphomas can all cause pancytopenia. ## Footnote These conditions often require specific evaluations for diagnosis.

Question 35

What specialized tests can provide valuable information about AA?

Answer 35

Bone marrow cytogenetics, mutation analysis, and immunophenotyping provide valuable information. ## Footnote These tests assess for clonal evolution and other hematologic disorders.

Question 36

What is the significance of telomere length analysis in children and young adults with AA?

Answer 36

It helps rule out telomere biology disorders. ## Footnote Telomere biology disorders can lead to premature aging and other complications.

Question 37

What clinical findings may suggest inherited bone marrow failure syndromes (IBMFS)?

Answer 37

Unexplained abnormalities of skin, nails, eyes, ears, short stature, or skeletal/genitourinary abnormalities may suggest IBMFS. ## Footnote IBMFS can have genetic components and familial patterns.

Question 38

What is myelofibrosis?

Answer 38

Myelofibrosis is a type of bone marrow disorder that can be caused by various factors including the progression of another subtype of MPN, rare cases of AML, HCL, metastatic cancers, and autoimmune disorders.

Question 39

What are some infectious diseases that can cause cytopenias?

Answer 39

Examples include: * Tuberculosis * Mycobacterial disorders * Brucellosis * Leishmaniasis

Question 40

True or False: Bacterial sepsis can lead to permanent bone marrow suppression.

Answer 40

False

Question 41

What must be distinguished from aplastic anemia (AA)?

Answer 41

Inherited (germline) bone marrow failure syndromes (IBMFS)

Question 42

At what age are IBMFS mostly seen?

Answer 42

In children, but increasingly recognized in adults.

Question 43

What percentage of children presenting with AA have an inherited etiology?

Answer 43

More than 25 percent

Question 44

What percentage of adults ≤40 years presenting with AA have an inherited etiology?

Answer 44

5 to 15 percent

Question 45

What family history might increase suspicion for an IBMFS?

Answer 45

A personal or family history of somatic abnormalities or unexplained blood disorders.

Question 46

What are some somatic abnormalities associated with IBMFS?

Answer 46

Examples include: * Short stature * Skeletal abnormalities * Skin/nail lesions * Idiopathic pulmonary fibrosis

Question 47

What is Fanconi anemia (FA)?

Answer 47

FA is characterized by pancytopenia, physical abnormalities, and predisposition to malignancies.

Question 48

What are some characteristic findings of dyskeratosis congenita (DC)?

Answer 48

Characteristic findings include: * Skin and nail abnormalities * Pulmonary fibrosis * Cancer predisposition

Question 49

What is Shwachman-Diamond syndrome (SDS)?

Answer 49

SDS classically presents with neutropenia, exocrine pancreatic dysfunction, and skeletal anomalies.

Question 50

What is congenital amegakaryocytic thrombocytopenia (CAMT)?

Answer 50

CAMT is caused by pathogenic gene variants of thrombopoietin or its receptor and manifests as thrombocytopenia and bleeding at birth.

Question 51

Fill in the blank: Many patients with an IBMFS require special surveillance for _______.

Answer 51

hematologic and/or nonhematologic malignancies

Question 52

What is the typical age of presentation for telomere biology disorders (TBD)?

Answer 52

Variable age of presentation

Question 53

What is a common feature of patients with SDS?

Answer 53

Pancytopenia, with neutropenia usually being the most prominent hematologic manifestation.

Question 54

True or False: Patients with an IBMFS are expected to have good responses to immune suppression therapy.

Answer 54

False