Pathology-Anemia V (Aplastic Anemia)

Front 1

Q: Describe the pathophysiology of aplastic anemia.

Back 1

-a syndrome (not a specific disease entitiy) of marrow failure associated with pancytopenia (anemia, neutropenia and thrombocytopenia)
-characterized by hypocellular bone marrow due to suppression or disappearance of multipotent myeloid stem cells

Front 2

Q: What is thought to cause suppression of stem cells?

Back 2

(1) it is thought that stem cells are first antigenically altered by exposure to drugs, infectious agents ro other unidentified environment insults, this evokes activated T cells to produce cytokines (interferon gamma and TNF) that prevent normal growth and proliferation
(2) results from a stem cell abnormality from genetic damage caused by marrow insults, this limits the proliferative and differentiative capacity of stem cells

Front 3

Q: Describe the morphology of aplastic anemia.

Back 3

-hypocellular bone marrow devoid of hematopoietic cells, often has only fat cells, fibrous stroma and scattered lymphocytes and plasma cells, also have granulocytopenia (reticulocytopenia) and thrombocytopenia
-get dry tap with bone marrow aspiration
-normocytic and normochromic, may be slight macrocytosis

Front 4

Q: Describe the clinical course of aplastic anemia.

Back 4

-initial manifestation depends on which cell line is affected predominantly, course of disease determined by severity of aplasia not etiology
-anemia causes weakness, pallor and dyspnea, thrombocytopenia can cause petechia (red spot caused by minor hemorrhage), ecchymoses (bruise), purpura (red discoloration of skin due to bleeding underskin, smaller than ecchymoses, but larger than petechia), granulocytopenia can manifest as frequent and persistent minor infections or onset of chills, fever and prostration
-splenomegaly is absent

Front 5

Q: What are some complications associated with aplastic anemia?

Back 5

-blood transfusions lead to hemosiderosis and hepatitis
-acute leukemia, myelodysplastic syndrome and PNH are all possible complications as well

Front 6

Q: What are the lab findings associated with aplastic anemia?

Back 6

-normochromic, normocytic anemia with varying degrees of pancytopenia
-hypocellular marrow with a low retic count
-INC serum iron because there is DEC uptake by the bone marrow and incorporation into RBCs

Front 7

Q: What is on the differential diagnosis of aplastic anemia?

Back 7

-preleukemia (if immature cells are seen) and leukemia (a potential complication with an incidence 2-5X population at large)
-if many lymphocytes are seen, a collagen-vascular disorder may be a suspected co-association
-PNH-test using leukocyte alkaline phosphatase (LAP) test to exclude PNH (in PNH, LAP is low)

Front 8

Q: How is aplastic anemia classified as severe?

Back 8

-patients classified as having severe aplasia have three of the four following criteria:
(1) platelet count < 20,000/uL
(2) reticulocyte count (corrected) <1% or according to Widmans <10,000/uL
(3) neutrophil count < 500/uL
(4) very severe if absolute neutrophil correct is < 200/uL, or according to Widmans a markedly hypocellular marrow with less than 20% hematopoietic cells remaining for longer than 3 weeks

Front 9

Q: Describe the milder form of aplastic anemia.

Back 9

-can also be called hypoplastic anemia, there is pancytopenia associated with it, but they do not meet the criteria for severe aplastic anemia

Front 10

Q: Describe the etiology of aplastic anemia.

Back 10

-can be acquired, hereditary or mechanistic
-most cases of aplastic anemia of “known” etiology follow exposure to chemical and drugs in a dose dependent manner, when remove then get cessation of anemia

Front 11

Q: Describe the acquired form of aplastic anemia.

Back 11

-approximately 50% are idiopathic, the remainder are considered to be secondary to chemicals, drugs, irradiation and infections

Front 12

Q: What are some examples of dose related agents that can cause aplastic anemia?

Back 12

-benzene, weed killers, insecticides (DDT, parathion), arsenicals (idiopathic)

Front 13

Q: What are some examples of drugs that cause acquired aplastic anemia?

Back 13

-chloramphenicol-does related type of bone marrow depression, characterized by cytoplasmic vacuolization in erythroid precursors, often in myeloid and other cells, reversible when drug discontinued, seldom or rarely fatal
-phenylbutazone
-chemotherapeutic agents (alkylating agents)

Front 14

Q: What are some examples of physical agents that cause acquired aplastic anemia?

Back 14

-whole body irradiation (LD50, about 300 rads), only 0.1% survive 700 rads

Front 15

Q: What are some examples of infections that cause acquired aplastic anemia?

Back 15

-viral hepatitis (especially C, which is the most common), follows infection by as long as half a year, usually affects 2-20 year age group,
-causes a very severe aplastic anemia with low survival (about 10%), the exact mechanism is however unknown

Front 16

Q: Describe the hereditary form of aplastic anemia.

Back 16

-is rare and usually assoacited with other genetic anomalies
-includes Fanconi’s anemia, Blackfan-Diamond syndrome and Pure Red Cell Aplasias

Front 17

Q: Describe Fanconi’s anemia.

Back 17

-is a rare autosomal recessive disorder, have bone marrow hypoplasia during the first decade of life
-it is associated with multiple congenital anomalies including hypoplasia of the kidney, spleen, bone and thumb
-can cause mental retardation

Front 18

Q: Describe the pathophysiology of Fanconi’s anemia.

Back 18

-caused by defects in a component of a multiprotein complex required for DNA repair

Front 19

Q: Describe pure red cell aplasias.

Back 19

-rare form of marrow failure characterized by a marked hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis, sometimes in association with thymoma (unknown why), there is no known linkage between thymus and normal RBC production

Front 20

Q: Describe the pathophysilogy of pure red cell aplasias.

Back 20

-related to autoimmunity against erythroid precursors and immunosuppressive therapy can be beneficial in such patients
-have sever anemia with reticulopenia

Front 21

Q: Describe Blackfan-Diamond Syndrome.

Back 21

-autosomal recessive pure red cell aplasia that occurs in the first two years of life, usually responds to steroids, have anemia with the rest of their blood cells normal, there is DEC erythroid progenitors in the marrow
-associated with craniofacial malformations, thumb and upper limb abnormalities, cardiac defects and cleft palate, INC risk of developing leukemias

Front 22

Q: What are some examples of mechanistic causes of aplastic anemia?

Back 22

-injury to stem cells (due to drugs, irradiation and some viruses)
-injury to microcirculation and stroma of the marrow (irradiation)
-infection (EBV, hepatitis)
-immunosuppression
-intrinsic defect of RBC cell development as seen with pure red cell aplasia
-autoimmune

Front 23

Q: Describe the approach to a patient with aplastic anemia.

Back 23

-the history is very important, want to know exposure to drugs, toxins and other possible marrow-suppressive agents (pesticides, cleaning solvents), occupational history, infections (hepatitis), X-ray, but remember about 50% are idiopathic
-physical exam-splenomegaly and lymphadenopathy (swollen lymph nodes) are usually not present

Front 24

Q: What is the treatment for aplastic anemia?

Back 24

-transfusion should be done in leukocyte depleted blood, but they should be limited to as few as possible, they should also not be from family members if considering bone marrow transplant
-bone marrow transplant