Aplastic anemia Flashcards
What type of anemia is characterized by failure of the bone marrow to produce peripheral blood cells and their progrenitors?
aplastic anemia
In aplastic anemia, the (…) stem cells do not repopulate in the bone marrow, resulting in severely diminished or absent comitted (…) cells
- hematopoietic stem cells
- progenitor cells
- The definition of aplastic anemia is a bone marrow failure syndrome defined by peripheral blood (….) and hypocellular bone marrow (…)
- This is also known as (…) which is the combination of not making enough WBCs, RBCs, and platelets
- What is the incidence of aplastic anemia?
- What is the predominant age of patients with aplastic anemia?
- pancytopenia; aplasia
- pancytopenia
- 2 cases per million
- 2 peaks: 15-25 year olds, or after 60 years
- Aplastic anemia can be either (…) or (…)
- What do patients present with?
- No cause (idiopathic) is identified in around (…)% of aplastic anemia cases
- acquired or congenital
- transfusion-dependent anemia, thrombocytopenia, and severe neutropenia with markedly reduced bone marrow cellularity (< 25% cellularity)
- 50%
- What is found in 30-80% of patients with idiopathic anemia?
- What do many of these patients respond to?
- abnormal expression of suppressor T cells
- immunosuppressive therapy
What are some causes of aplastic anemia?
- inherited factors
- pregnancy
- idiopathic cause
What inherited factors can lead to aplastic anemia?
- Fanconi’s anemia
- reticular dysgenesis
- congenital dyskeratosis
- non-hematologic syndromes (down syndrome, etc)
- diamond-blackfan syndrome
What is the most common inherited form of aplastic anemia?
Fanconi’s anemia
What are some common acquired factors that can lead to (or increase risk of) aplastic anemia?
- toxins
- drugs
- ionizing radiation
- infections
- nutritional deficiencies
What infections can lead to aplastic anemia?
- hepatitis C
- HIV
- EBV
- parvovirus B19
- Some forms of acquired aplastic anemia are associated with an associated (…) or (…)
- A small percentage of patients with (…) can transform into aplastic anemia
- thymoma or autoimmune disorder (SLE)
- paroxysmal nocturnal hemoglobinuria (PNH)
What is the differential diagnosis of pancytopenia (aplastic anemia) with hypocellular bone marrow?
- acquired aplastic anemia
- inherited aplastic anemia
- hypoplastic MDS (myelodysplasia)
- hypoplastic AML (acute myeloid leukemia)
- Aplastic anemia is usually present with manifestations of (…)
- What are some symptoms of aplastic anemia?
- What are signs of aplastic anemia on a physical exam?
- low blood counts
- low platelets, anemia, neutropenia
- low platelets, anemia
What symptoms are associated with low platelets, anemia, and neutropenia d/t aplastic anemia?
- low platelets: epistaxis, bleeding gums, bruising w/ mild or no trauma, menorrhagia
- anemia: fatigue, dyspnea on mild exertion
- neutropenia: less commonly present with ongoing bacterial/fungal infection
What signs are associated with low platelets and anemia d/t aplastic anemia?
- low platelets: petechiae (palatal or cutaneous), ecchymoses, and epistaxis
- anemia: pallor
Autoimmune aplastic anemia may have (…)
hepatosplenomegaly
- The work-up of aplastic anemia primarily consists of what?
- This generally shows paucity or absence of (…) and (…) precursor cells
- Patients with pure red cell aplasia demonstrate only an absence of (…) precursors in the marrow
- bone marrow aspiration and biopsy
- erythropoietic and myelopoietic precursor cells
- RBC precursors
What will a CBC show if a patient has aplastic anemia?
- pancytopenia
- macrocytosis and toxic granulation of neutrophils
- isolated cytopenias in eary stages
What will a reticulocyte count show if a patient has aplastic anemia?
reticulocytopenia; precursors are gone
What are some additional laboratory tests you can do if a patient has suspected aplastic anemia?
- Ham test
- peripheral blood flow cytometry to exclude PNH
- evaluaton for Hep C
What test shows lysis of the patient’s RBCs in acidified fresh serum, which is specific for paroxysmal nocturnal hemoglobinuria?
Ham test
What type of imaging can you do to evaluate aplastic anemia?
MRI
What imaging technique has a spin-echo sequence that helps with the study of bone marrow disease, and the high fat content of aplastic marrow can be easily seen on this?
MRI
- What should you do if a patient is sound to have pancytopenia?
- If these are negative, what should you do next?
- examine blood smear; evaluate for signs of B12/folate deficiency
- examine bone marrow biopsy and aspirate to see overall cellularity, cellular morphology, cytogenetics
- If there is no hypoceullarity on bone marrow biopsy and aspirate, what can be ruled out?
- If there is hypocellularity, what do you look at next?
- If this is yes, what is the diagnosis?
- If this is no, what is the diagnosis?
- aplastic anemia
- presence of myelodysplastic morphology or clonal cytogenetic abnormalities
- myelodysplasia
- aplastic anemia
What will a peripheral blood smear show in the diagnosis of aplastic anemia?
- normochromic-normocytic RBCs
- normal MCV and MCH
- pancytopenia
- no abnormal cells
What will a bone marrow evaluation show in the diagnosis of aplastic anemia?
- hypocellular (decreased precursor cells) bone marrow with increased fat spaces, lymph cells, plasma cells, macrophages, mast cells
In aplastic anemia, it is important with bone marrow assessment to obtain both a (…) and (…)
biopsy and aspiration
- What best assesses overall bone marrow cellularity and provides the most sensitive evidence of some infiltrative processes in aplastic anemia?
- What can be examined microscopically for the presence of abnormal cells but also provides cells for cytogenetic analyses (which can provide evidence supporting hypoplastic myelodysplasia and acute leukemia?
- biopsy
- aspirated sample from bone marrow
What severity of aplastic anemia is this describing:
- bone marrow cellularity <25%
- peripheral blood neutrophil count < 500
- peripheral blood platelet count < 20,000
- peripheral blood corrected reticulocytes < 1%
severe
What severity of aplastic anemia is this describing:
- peripheral blood neutrophil count < 200
very severe
What severity of aplastic anemia is this describing:
- hypocellular bone marrow with peripheral blood cytopenias
non-severe
- With acute treatment of aplastic anemia, aggressive treatment of neutropenic fever is done with (…)
- You can also administer (…) and (…) transfusions prn, but, it is important to avoid in (…) transplant candidates
- parenteral broad-spectrum antibiotics
- platelet and RBC transfusions
- bone marrow transplant candidates
What is the acute treatment of moderate aplastic anemia?
- observation/treatment prn
- ATG: antithymocyte globulin
- non-responders: CSA (cyclosporine A)
- What does ATG (antithymocyte globulin) do in acute treatment of moderate aplastic anemia?
- How is this usually given? How long?
- kills T-lymphocytes, allowing bone marrow to resupply stem cells
- IV for 8-12 hours a day for 4 days
What does CSA (cyclosporine A) do in acute treatment of moderate aplastic anemia?
prevents T lymphocytes from becoming active
What is the acute treatment of severe aplastic anemia in children and young adults?
- human leukocyte antigen (HLA) typing
- if no sibling for bone marrow transplant, ATC and CSA (70% effective if used together)
- What is the acute treatment of severe disease of aplastic anemia in older adults?
- When should you see a blood count improvement?
- ATG and CSA first-line
- at 3-6 months
If patients are not responding to acute treatment for severe aplastic anemia, what is considered?
- non-match BMT, androgens and/or 2nd immunosuppression
- allogenic hematopoietic stem cell transplantation (HSCT)
What is the non-pharmocological acute treatment for aplastic anemia?
discontinue offending agents
What can be a curative chronic treatment for those with aplastic anemia?
allogenic bone marrow transplantation (ABMT) from an HLA-matches sibling donor
- How can patients without siblings be chronically treated for aplastic anemia?
- What is the risk they are taking with this?
- can be treated with an unrelated match (bone marrow transplant)
- mortality rate is higher
- In a bone marrow transplant, what affects mortality?
- The longer the (…) is associated with an increased 5 year survival?
- telomere mutation characteristics
- telomere length
Pertaining to chronic treatment of aplastic anemia:
- (…) therapy with (…) is an effective alternative therapy is non-candidate for ABMT (bone marrow transplant)
- (…) also have a role in treatment
- (…) such as (…) are effective 2nd line agents in aplastic anemia treatment
- What can improve hematopoiesis in refractory severe aplastic anemia?
- immunosuppressive therapy with ATG
- ISAs (beta blockers)
- androgens such as danazol
- oral thrombopoietin mimetic, eltrombopag (tx for thrombocytopenia)
What ISAs have a role in the chronic treatment of aplastic anemia?
- cyclosporine
- cyclophosphamide
- corticosteroids
What is the preferred treatment for children and young adults (<40) with aplastic anemia with an allele-level HLA-matched doner, especially if from a sibling donor?
hematopoietic cell transplantation
(…) and (…) have been used for those patients with aplastic anemia who are unable to have a hematopoietic cell transplant
ATG and cyclosporine immunotherapy
- What is common with ATG and cyclosporine treatment with patients with aplastic anemia that receive this treatment?
- However, long term outlook, as a result of disease (…) or evolution to (…) or (…) is poor
- remission
- relapse or evolution to oligobastic or polyblastic (acute) myelogenous leukemia
Approximately 15% of patients with aplastic anemia treated with immunotherapy express an abnormal (…) or an overt (…)
- karyotype
- clonal myeloid neoplasm (PNH or oligoblastic/polyblastic acute myelogenous leukemia)
- Relapsed patients who have already taken immunotherapy for aplastic anemia may respond to a second administration of (…) or (…)
- Often, if (…) or (…) is used initially, the alternative is used in retreatment, if available
- ATG and cyclosporine
- horse or rabbit ATG
- (…) alone has resulted in a favorable hematologic response in approximately 50% of patients treated who have aplastic anemia
- In adults, 150 mg/day is administered for (…) weeks is considered appropriate; lower doses are used in (…) and children and patients of (…) descent
- eltrombopag
- 24 weeks
- adolescents
- Asian
- Up to 75% of patients with aplastic anemia response to immunosuppressive therapy with (…), (…), and (…)
- The most recent update for bone marrow transplantation statistics reports long-term survival rate of (…)%
- What are the major complications of ABMT?
- All patients with aplastic anemia should be referred to (…)
- antithymocyte globin (ATG), corticosteroids, and cyclosporine
- 80%
- graft rejection and graft-vs-host disease
- hematology
A person is admitted with an autoimmune disease directed against the hematopoietic stem cells. This will produce:
1. aplastic anemia
2. iron-deficiency anemia
3. sideroblastic anemia
4. fanconi anemia
- aplastic anemia
In a patient with pancytopenia, which of the following abnormalities in the peripheral blood smear would provide a useful indicator that the cause of the pancytopenia is aplastic anemia?
1. hypersegmented polymorphononuclear leukocytes
2. nucleated red cells
3. teardrop-shaped red cells
4. giant platelets
5. none of the above
- none of the above: peripheral smear is usually normal
Which is showing the bone parrow of a person with aplastic anemia?
right
Which is showing a peripheral blood smear of a patient with aplastic anemia?
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