SINDROMES DE INSUFICIENCIA HEMATOPOIETICA

Question 1

CARACTERIZE ANEMIA APLASICA

Answer 1

pancytopenia in association with bone marrow hypoplasia/aplasia, most often due to immune injury to multipotent hematopoietic stem cells

Question 2

AA

Answer 2

Loss of hematopoietic stem cells (HSC) is a defining feature of AA.

Question 3

CAUSAS DE AA

Answer 3

• Autoimmune mechanisms

●Direct injury to HSCs (eg, by drugs, chemicals, irradiation)

●Viral infection

●Clonal and genetic disorders - HPN, SMD, LMA

Question 4

CITE AS CAUSAS DE AA POR GRUPO

Answer 4

1 - RADIACAO- TTO PARA NEOPLASIAS
2 - DROGAS > CARBAMAZEPINA, FENITOINA, 
  ATB> SULFONAMIDAS, CLORANFENICOL
  AINES - INDOMETACINA
  ANTITIREOIDIANOS > METIMAZOL E PTU
3 - SUBSTANCIAS QUIMICAS -> BENZENO, SOLVENTES
4- VIRUS > EBV, HPATITE SORONEGATIVA, HIV
5- LES, GVHD
6- HPN, ANOREXIA NERVOSA, GRAVIDEZ

Question 5

RELACIONE A AA COM HPN

Answer 5

Expanded populations of blood cells with the PNH defect have been detected by flow cytometry in approximately half of patients with AA [63]. The abnormal blood cells are thought to initiate an immune response that damages HSCs and other hematopoietic precursors

Question 6

ANEMIA DE FANCONI

Answer 6

Fanconi anemia — The most common form of inherited AA is Fanconi anemia (FA), a condition characterized by pancytopenia, predisposition to malignancy, and physical abnormalities (eg, short stature, microcephaly, developmental delay, café-au-lait skin lesions, other characteristic malformations).

Question 7

SINTOMAS DE AA

Answer 7

INFECÇOES DE REPETICAO
HEMORRAGIAS DE MUCOSA, MONORRAGIA
FADIGA E ACHADOS CARDIOPULMONARES PELA ANEMIA

Question 8

COMO FAZER DIAGNOSTICO DE ANEMIA APLASTICA

Answer 8

AA is defined as pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate or marrow fibrosis.

BX DE MO
The bone marrow is profoundly hypocellular with a decrease in all elements; the marrow space is composed mostly of fat cells and marrow stroma

Residual hematopoietic cells are morphologically normal and hematopoiesis is not megaloblastic.

Infiltration of the bone marrow with malignant cells or fibrosis is not present.
CELULARIDADE<25%

Question 9

AA SEVERA

Answer 9

Severe AA — Diagnosis of severe aplastic anemia (SAA) requires both of the following criteria [75]:
● Bone marrow cellularity <25 percent (or 25 to 50 percent if <30 percent of residual cells are hematopoietic)

● At least two of the following:

• Peripheral blood absolute neutrophil count (ANC) <500/microL (<0.5 X 109/L)
• Peripheral blood platelet count <20,000/microL
• Peripheral blood reticulocyte count <20,000/microL

Question 10

DDIFERENCIAL DA ANEMIA APLASTICA

- ANEMIA MEGALOBLASTICA

Answer 10

Megaloblastic anemia (eg, pernicious anemia, malnutrition) can cause profound pancytopenia and bone marrow hypoplasia, most commonly due to deficiencies of vitamin B12 and/or folate. Megaloblastic anemia is characterized by the presence of hypersegmented neutrophils and macro-ovalocytes on the peripheral blood smear and megaloblastic changes in the bone marrow examination; serum levels of vitamin B12 and/or folate can confirm these diagnoses

Question 11

DDIFERENCIAL DA ANEMIA APLASTICA

- DESORDENS INFILTRATIVAS

Answer 11

Infiltration of the bone marrow by fibrosis (eg, myeloproliferative neoplasms such as primary myelofibrosis), malignancies (eg, MDS, AML, lymphoma, multiple myeloma, carcinoma), or infectious agents (eg, tuberculosis, fungi) may cause pancytopenia by bone marrow replacement and/or sequestration/redistribution of blood cells. These disorders can usually be distinguished from AA by the presence of myelophthisic changes on the peripheral blood smear (eg, schistocytes, nucleated red blood cells) and morphologic, cytogenetic, and/or molecular abnormalities of the bone marrow

Question 12

COMO DEFINIR PANCITOPENIA

Answer 12

●Red blood cells – Hemoglobin <12 g/dL for non-pregnant women and <13 g/dL for men

● White blood cells – Because neutrophils constitute the majority of leukocytes in the peripheral blood and bone marrow, nearly all cases of low white blood cells (leukopenia) manifest as neutropenia.

Absolute neutrophil count (ANC) <1800/microL – Calculated as the total white blood cells/microL x (percent [polymorphonuclear cells + bands] ÷ 100) (calculator 1)

● Platelets – Platelet count <150,000/microL

Question 13

CITE OS TRES GRUPOS DE CAUSAS DE PANCITOPENIA

Answer 13

Bone marrow infiltration/replacement

Bone marrow aplasia

Blood cell destruction or sequestration

Question 14

CAUSAS DE PANCITOPENIA POR INFILTRACAO ; OCUPACAO MEDULAR

Answer 14

Bone marrow infiltration/replacement – Such disorders include hematologic malignancies (eg, leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes), metastatic cancer, myelofibrosis, and infectious diseases (eg, miliary tuberculosis, fungal infections).

Question 15

CAUSAS DE PANCITOPENIA POR APLASIA

Answer 15

Nutritional disorders (eg, deficiencies of vitamin B12 or folate), aplastic anemia, infectious diseases (eg, HIV, viral hepatitis, parvovirus B19), immune destruction, and medications are among the causes of marrow aplasia.

Question 16

CAUSAS DE PANCITOPENIA POR DESTRUCAO OU SEQUESTRO DE CELS SANGUINEAS

Answer 16

CIVD, PTT, HEMATOPOIESE INEFICAZ ( SMD, SD MEGALOBLASTICAS);

HIPERESPLENISMO - CIRROSE, DOENCAS DE DEPOSITO, LINFOMA

Question 17

O QUE É APLASIA DE SERIE VERMELHA PURA

Answer 17

The cardinal clinical feature in PRCA is isolated, severe anemia without an adequate reticulocyte response. Examination of the bone marrow shows an absence of erythrocyte precursors.

Question 18

CITE CAUSAS DE APLASIA DE SERIE VERMELHA

Answer 18

• INF POR PARVOVIRUS B19
  TIMOMA
  DOENCAS AI - LES , AR
  TUMORES SOLIDOS

Question 19

TTO DE INFECCAO POR PARVOVIRUS B19 EM PACIENTES IMUNOCOMPROMETIDOS OU COM HEMOLISE CRONICA

Answer 19

IVIG

Question 20

TTO DE AA

Answer 20

CICLOSPORINA
IMUNOGLOBULINA ANTI-TIMOCITO
Allogeneic HSCT is a potentially curative therapy and should be considered for those younger than 50 years who have compatible donors.

Question 21

TTO DE APLASIA DE SERIE VERMELHA

Answer 21

CICLOSPORINA OU CICLOFOSFAMIDA + PREDNISONA

Question 22

CAUSAS DE NEUTROPENIA

Answer 22

• HIV, CMV, EBV
• AINES, CARBAMAZEPINA, FENITOINA, PTU, CEFALOSPORINAS, SMT-TMP, ANTIPSICOTICOS
  (IDIOSSINCRATICAS)
• AI- LES E AR
• DEFICIENCIA DE B12 E FOLATO
• SMD

Question 23

CARACTERIZE A SMD

Answer 23

Dysplastic and ineffective blood cell production and a variable risk of transformation to acute leukemia.
Patients with MDS have varying reductions in the production of red blood cells, platelets, and mature granulocytes that may also exhibit functional (ie, qualitative) defects; these abnormalities often result in anemia, bleeding, and increased risk of infection.

Question 24

Cite alguns achados no esfregaço periferico de um paciente com SMD

Answer 24

• Hemacias : Ovalomacrocitose, eliptocitos, acantocitos (alteracoes em prot do citoesqueleto), Corpos de Howell- Jolly, hemacias nucleadas, pontilhado basofilico
• Neutrofilos : Hiposegmentacao nuclear e hipogranulacao
  Anormalidade de Pseudo- Pelger- Huet

Question 25

Cite a anormalidade cromossomial com bom progrnostico na SMD

Answer 25

delecao do 5q

Question 26

Na SMD os blastos em periferia por definicao correspondem a quantos %?

Answer 26

<20%
AREB tipo 1: 5-9%
AREB tipo 2: 10-19%

Question 27

Existem achados cromossomiais que independente do numero de blastos definem LMA
Quais sao?

Answer 27

t(8;21)
inv(16)
t(15;17)

Question 28

Assim como algumas anormalidades cromossomiais sugerem SMD. Cite 3

pense em delecoes

Answer 28

Similarly, the presence of one of the following chromosomal abnormalities is presumptive evidence of MDS in patients with otherwise unexplained refractory cytopenia and no morphologic evidence of dysplasia [128]:
● -7/del(7q)
● -5/del(5q)
● del(13q)
● del(11q)
● del(12p) or t(12p)
● del(9q)

Question 29

Dx de SMD

Answer 29

Otherwise unexplained quantitative changes in one or more of the blood and bone marrow elements (ie, red cells, granulocytes, platelets). The values used to define cytopenia are: hemoglobin <10 g/dL (100 g/L); absolute neutrophil count <1.8 x 109/L (<1800/microL); platelets <100 x 109/L (<100,000/microL).

●
Morphologic evidence of significant dysplasia (ie, ≥10 percent of erythroid precursors, granulocytes, or megakaryocytes) upon visual inspection of the peripheral blood smear, bone marrow aspirate, and bone marrow biopsy in the absence of other causes of dysplasia (table 3). In the absence of morphologic evidence of dysplasia, a presumptive diagnosis of MDS can be made in patients with otherwise unexplained refractory cytopenia in the presence of certain genetic abnormalities.

●
Blast forms account for less than 20 percent of the total nucleated cells of the bone marrow aspirate and peripheral blood. Cases with higher blast percentages are considered to be acute myeloid leukemia (AML). In addition, the presence of myeloid sarcoma (extramedullary AML) or certain genetic abnormalities, such as those with t(8;21), inv(16), or t(15;17), are considered diagnostic of AML, irrespective of the blast cell count.

Question 30

Indicacoes de Tto da SMD

Answer 30

Anemia sintomática- Transfusoes de CH
Trombocitopenia sintomática
Neutropenia sintomática- ATB

• Fatores de crescimento , decitabina, lenalidomida
• • TMO + QT