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Flashcards in Approach to Cytopenias Deck (54):
1

What is/are common symptoms of pancytopenia?

A) mouth sores
B) fever
C) shortness of breath
D) All of the above

D) All of the above

mouth sores from low platelets causing purpura

2

What is the most common etiology of aplastic anemia?
A) Benzene
B) Chloramphenicol
C) Parvovirus
D) Idiopathic

D) Idiopathic

3

T or F. The mechanism that cause pancytopenia are bone marrow failure and destruction of blood cells in the peripheral blood

T.

4

Pancytopenia includes what?

- blood cells (anemia)
- white blood cells (leukopenia)
- platelets (thrombocytopenia)

5

What are the symptoms of anemia?

- dyspnea
- chest pain
- fatigue

6

What are the symptoms of leukopenia/neutropenia?

-fever
-infection
-mouth sores

7

What are the symptoms of thrombocytopenia?

bleeding

8

What are the two basic causes of pancytopenia?

- increased destruction
- decreased production

9

What are some possible causes of increased destruction leading to pancytopenia?

-immune destruction (ITP)
-sepsis
-hypersplenism

10

What are some possible causes of decreased production leading to pancytopenia?

-myelodysplasia
-marrow infiltrate
-B12 deficiency
-asplastic anemia
-drugs
-viruses (hep, HIV)
-radiation

11

What things could lead to a hypercellular bone marrow in someone who is pancytopenic?

-bone marrow infiltration (heme malignancies, carcinoma, B12/folate deficiency)

12

What things could lead to a hypocellular none marrow?

-aplastic anemia

13

What are congenital causes of aplastic anemia?

-Fanconi's anemia
-Familial aplastic anemia

14

What are some acquired causes of aplastic anemia?

-idiopathic (most common)
-drugs/chemical
-radiation
-viruses
-pregnancy (rare)
-PNH
-myelodysplastic syndrome

15

What does aplastic anemia result in?

Aplastic anemia is a severe, life threatening syndrome in which production of erythrocytes, WBCs, and platelets has failed (pperipheral ancytopenia)

16

What patient population is common for aplastic anemia?

all age groups and both genders

17

Asplastic anemia is characterized by what?

-peripheral pancytopenia
-hypocellular bone marrow

18

What is a primary mechanism of idiopathic aplastic anemia?

Immune mediated destruction of hematopoietic stem cells

19

What is the pathophysiology of aplastic anemia?

a reduction in or depletion of hematopoietic precursor stem cells which results in decreased production of all cell lines.

This is what leads to the peripheral pancytopenia

20

What could cause a reduction in or depletion of hematopoietic precursor stem cells with decreased production of all cell lines?

This may be due to quantitative or qualitative damage to the pluripotential stem cell

or the result of a defective bone marrow microenvironment (no differentiation cytokines present)

or from cellular or humoral immunosuppression of hematopoiesis.

21

When does Fanconi anemia become symptomatic? What is it associated with?

~5 y/o
-associated with progressive bone marrow hypoplasia

22

What congenital clinical manifestations are seen in Fanconi anemia?

skin hyperpigmentation and small stature

23

What is Familial aplastic anemia?

a subset of Fanconi’s anemia in which the obvious congenital defects are absent but bone marrow is present. These paitents can present at older ages.

24

T or F. Most cases of aplastic anemia are idiopathic and there is no history of exposure to substances known to be causative agents of the disease

T.

25

How does ionizing radiation cause aplastic anemia?


Exposure to ionizing radiation – hematopoietic cells are especially susceptible to ionizing radiation. Whole body radiation of 300-500 rads can completely wipe out the bone marrow. With sublethal doses, the bone marrow eventually recovers.

26

What chemicals can cause aplastic anemia?

- chemical agents with a benzene ring
- chemotherapeutic agents
- certain insecticides

27

What drugs can cause aplastic anemia?

chloramphenicol or quinacrine

These are Idiosyncratic reactions

28

What kinds of infections can cause aplastic anemia?

viral or bacterial
- infectious mononucleosis
- infectious hepatitis
- parvovirus/ CMV
- miliary TB

29

Lab findings with aplastic anemia?

-Severe pancytopenia with relative lymphocytosis (lymphocytes live a longer time)

-Normochromic/macrocytic, normocytic RBCs (may be slightly macrocytic)

-Mild to moderate anisocytosis and poikilocytosis

-Decreased reticulocyte count

-Hypocellular bone marrow with > 70% yellow marrow

30

What is/are treatment options for aplastic anemia?

withdrawal of potentially offending agents

supportive care (eg, transfusion, antibiotics),

immunosuppressive regimens

hematopoietic cell transplantation (HSCT)

31

What are some Immunosuppressive alternatives for aplastic anemias?

-anti-thymocyte globulin,
-cyclosporine,
-steroids

This observation suggests that auto-immune destruction of hematopoietic stem cells is a primary cause of acquired idiopathic aplastic anemia

32

What is pure red cell aplasia?

a selective decrease in erythroid precursor cells in the bone marrow. WBCs and platlets are unaffected

33

What are some causes of pure red cell aplasia?

- viral or bacterial infections

- Patients with hemolytic anemias may suddenly halt erythropoiesis

- Patients with thymoma – T-cell mediated responses against bone marrow erythroblasts or erythropoietin are sometimes produced

34

What is the treatment for pure red cell aplasia?

-supportive care and immunosuppression

35

What is the primary difference between myelodysplastic syndrome and aplastic anemia?

presence or absence of neoplastic cells in the bone marrow

36

What are myelodysplastic syndromes (MDS)?

are primary, neoplastic stem cell disorders that tend to terminate in acute leukemia.

37

How does the bone marrow look in myelodysplastic syndromes?

-normocellular, or hypercellular with evidence of qualitative abnormalities in one or more cell lines resulting in ineffective erythropoiesis and/or granulopoiesis and/or megakaryopoiesis.

-ringed sideroblasts and other dysplastic changes

38

What does the peripheral blood show in myelodysplastic syndromes?

dysplastic (abnormality in development) cells including nucleated RBCs, oval macrocytes, pseudo-Pelger-Huet PMNs (hyposegmented neutrophils) with hyperchromatin clumping, hypogranulated neutrophils, and giant bizarre platelets.

39

What do MDS arise from?

mutations in the multi-potent bone marrow stem cell

Differentiation of blood precursor cells is impaired, and there is a significant increase in levels of apoptotic cell death in bone marrow cells

Clonal expansion of the abnormal cells results in the production of cells which have lost the ability to differentiate. (the presence of a neoplastic clone differentiates from aplastic anemia)

If the overall percentage of bone marrow blasts rises over a particular cutoff (20% for WHO and 30% for FAB) then transformation to acute myelogenous leukemia (AML) is said to have occurred.

40

What are the main goals of treatment for MDS?

The goals of therapy are to control symptoms, improve quality of life, improve overall survival, and decrease progression to AML

41

What is the treatment for MDS?

Supportive care with blood product support and hematopoeitic growth factors (e.g. EPO) is the mainstay of therapy

Chemotherapy with the hypomethylating agents 5-azacytidine and decitabine has been shown to decrease blood transfusion requirements and to retard the progression of MDS to AML and increase survival

42

What is a good treatment option for MDS with del(5q)?

lenalidomide

43

Can MDS be cured?

Hematopoetic Stem cell transplantation (HSCT), particularly in younger patients (i.e. less than 60 years of age), more severely affected patients, offers the potential for curative therapy

44

What is an HSCT?

The transplantation of hematopoietic progenitor cells that have the ability to proliferate and repopulate the marrow spaces

45

What is an autologous HSCT?

Uses stem cells collected from a patient, stored in a freezer to be reinfused or transplanted at a later date following high dose chemotherapy.

Because infused stem cells belong to the recipient, there is minimal to no risk of a reaction between the cells and the donor. Because of this, the overall risk of morbidity and mortality from Auto SCT is low

46

Auto SCT allows the use of _______ in a patient.

high dose chemotherapy

A dose that would normally wipe out a patient’s hematopoetic stem cells. The stored stem cells are able to rescue the patient’s hematopoetic system after chemotherapy

47

Auto SCT is used mainly in what?

treatment of lymphomas and multiple myeloma

48

What is an allogeneic SCT?

Uses related or unrelated HLA (human leukocyte antigen) matched donors as the source of stem cell

Matching is performed on the basis of variability at three or more loci of the (HLA) gene, and a perfect match at these loci is preferred to prevent graft versus host disease (GVHD).

49

Allogeneic SCT GVHD risk.

Even if there is a good match at these critical alleles, GVHD can still occur, and the recipient will require immunosuppressive medications. This incidence of GVHD significantly increases the risk of morbidity and mortality in patients who undergo allogeneic stem cell transplantation vs autologous stem cell transplant.

50

What are the advantages of allogeneic SCT vs Auto SCT?

Can be used when recipient/patient’s bone marrow fails such as if they have aplastic anemia or myelodysplastic syndrome

When recipient has certain disease such as leukemia and lymphoma, the donor cells can attack these tumor cells via graft versus disease effect to prevent relapse of the tumor.

51

Overview of Allogeneic HSCT

1) Collection- stem cells are collected from donor's bone marrow or peripheral blood

2) Processing- BM or blood is processed to isolate, concentrate, and prepare stem cells for storage

3) Stem cells are preserved by freezing at very low temps in protective solutions (DMSO used) to keep them alive

4) Chemo- patients are treated with chemo and/or radiation to destroy unwanted cancer and develop bone marrow failure

5) Infusion of stem cells

6) Maintain transplanted cells with immunosuppressant therapy

52

18 year old African American male presented to Methodist Hospital with complaint of fatigue and ‘passing out’
On presentation, wbc = 0.8, hgb = 5.5, platelets = 40,000
No family history of blood problems
Exam was unremarkable
Reticulocyte count less than 2%
hypocellular BM

Diagnosed with severe aplastic anemia

Treated with Anti-thymocyte globulin, steroids, and cyclosporine

Blood counts did not improve. He required blood and platelet transfusion 1-2 times/week

No infectious complications, however

53

What is the next step in this patient's treatment?

HLA trying of the patient's siblings

54

Mild GVHD disease can actually help prognosis as the transplant could help target the leukemia

Mild GVHD disease can actually help prognosis as the transplant could help target the leukemia