9) Aplastic and hypoproliferative anemias Flashcards
morphologic and BM characteristics of hypoproliferative/aplastic anemias
normocytic normochromic
hypocellular marrow
aplasia —pancytopenia (precursor affected)
parts of aplastic anemia dx (4)
- BM <25% cellularity
- ANC <0.5
- platelets <20
- corrected retic <1% (no compensation)
2 age groups affected by aplastic anemia
young (<20) - usually idiopathic
older (>60) - usually secondary
4 general pathophysiologies of aplastic anemia
- immune suppression (autoimmunity)
- abnormal/deficient HSCs
- bone marrow matrix defects
- deficient GFs (not sole cause)
2 general categories of aplastic anemia and causes in both
Acquired
Idiopathic
Drugs
Chemicals
Radiation
Infectious agents
Metabolic errors
Paroxysmal nocturnal hemoglobinuria
Constitutional/congenital
Fanconi’s anemia
Familial aplastic anemia
chloramphenicol
phenobutazone
acquired aplastic anemia
benzene derivatives (inhibit DNA synth)
acquired aplastic anemia
this treatment does not work for radiation-related aplasic anemia
why?
BM transplant
the anemia is due to a matrix change in the BM
infectious agents that can cause aplastic anemia
TB
EBV
CMV
HIV
parvovirus (limited to RBCs)
hepatitis (not known viruses)
infection-related aplastic anemia that is often fatal
hepatitis
metabolic errors that lead to accumulation of ketones and glycine can cause…
aplastic anemia
explain PNH
membrane abnormality
lipid that protects cells from complement lysis is absent
cells lyse at night when pH in kidney drops
autosomal recessive, slowly progressive aplastic anemia
Fanconi’s anemia
Fanconi’s anemia s/s
- bone dysplasia
- renal abnormalities
- organ malformations
- mental retardation
- dwarfism
- microcephaly
- hypogonadism
- skin hyperpigmentation
- thumb abnormalities
- strabismus
Fanconi’s effects on blood cells
- platelets fall first, and get critically low
- decrease in granulocytes
- neutrophils get large pink granules
- macrocytosis occurs before anemia
Fanconi’s therapies
- Androgen tx — reverse pancytopenia for several years
- BM transplant
Fanconi’s median survival age
30
aplastic anemia
specific inheritance pattern uknown
familial aplastic anemia
clinical findings of aplastic anemia
- insidious, gradual progression
- bleeding, anemia, infection
- usually no organomegaly
PB findings in aplastic anemia
- pancytopenia
- normocytic, normochromic
- corrected retic <1%, no compensation
- platelets decrease first, then neutrophils, then WBCs
- relative lymphocytosis due to decreased neutros
- neutrophil granules that are large and stain dark red
BM findings in aplastic anemia
- hypocellular, >70% fat —dry tap
- macrophages with Fe, but no siderocytes
dry tap
aplastic anemia
fetal characteristics of RBCs (Hgb F, i antigens)
aplastic anemia
Diamond-Blackfan syndrome
iron and EPO in aplastic anemia
EPO ↑
serum Fe ↑
% sat ↑
cure for aplastic anemia
BM transplant
survival rate for aplastic anemia
2 years for 60-90%
3 other disorders important to differentially diagnose from aplastic anemia
- myelophthisic anemia
- myelodysplastic syndrome (MDS)
- congenital dyserythropoietic anemia (CDA)
characteristics of myelophthisic anemia
- BM “crowded out” by fibrotic, granulomatous or neoplastic cells
- tear drops
- giant platelets
- poik
- nRBCs and left shift (leukoerythroblastosis)
characteristics of MDS
- “preleukemia”, tends to end in leukemia
- cytopenia with ↓ retic
- BM is normocellular or hypercellular, with dyshematopoiesis (weird BM cells) —cells lyse before release into PB
characteristics of CDA
- abnormal and ineffective erythropoiesis
- rare, familial, refractory anemia
- BM is normocellular or hypocellular
- pancytopenia
- myeloblasts and promyelocytes
- RBC precursors multinucleated
- macrocytic anemia
3 types of pure red cell aplasia
- acquired acute PRC aplasia
- acquired chronic PRC aplasia
- diamond-blackfan syndrome
general s/s of pure red cell aplasia
- ↓ RBC, Hct, Hgb
- Corrected retic <1%
- ↑M:E ratio in BM
- ↑EPO
parvovirus B19, Fifth disease
hepatitis (poor prognosis)
other infections
acquired acute pure red cell aplasia
worst prognosis for acquired acute PRC aplasia
with hepatitis
transient erythroblastopenia of childhood is a type of…
acquired acute PRC aplasia
autoimmune disorders
thymoma
middle age
acquired chronic PRC aplasia
rare, congenital, progressive RBC aplasia
diamond-blackfan syndrome
characteristics of diamond-blackfan
- very young children
- severe anemia
- ↑i Ag, ↑ Hgb F
- 100% sat, ↑ serum Fe, ↑ ferritin
- ↑EPO
- minor abnormalities of head and arms
distinguish Diamond-blackfan from TEC
↑i Ag, ↑ Hgb F found only in diamond-blackfan
most common cause of non-aplastic, non-pure RBC hypoproliferative anemias
↓ EPO
can result in normo/normo, megaloblastic, or micro/hypo anemia
how?
renal disease
↓ EPO —normo/normo
dialysis ↓ folate —megaloblastic
dialysis ↓ iron —micro/hypo IDA
high BUN and creatinine often causes…
burr cells
how can endocrine abnormalities cause a hypoproliferative normo/normo anemia?
hypothyroidism/hypopituitarism
↓ O2 demand in tissues
indirectly ↓ EPO
anemia occuring in patients with chronic infection, inflammation, or neoplasms
anemia of chronic disease/inflammation
iron in ACD patients
↓ serum Fe
normal or ↑ Fe stores
↑ ferritin
↓ TIBC
second most common anemia
ACD
3 mechanisms of ACD
- cytokines released by inflammatory response inhibit EPO, and cell response to EPO
- hepcidin blocks Fe mobilization, so macrophages are unable to give it up for use
- early phagocytosis of good RBCs leads to shortened lifespan (extracorpuscular factors)
PB findings in ACD
- mild anemia (Hgb ≥9)
- normo/normo, but eventually micro/hypo
- RPI <2
- normal WBC, normal platelets
BM findings in ACD
not necessary for dx
- ↑ M:E ratio
- ↑ hemosiderin in macrophages
malignancy can cause a ————– anemia when it infiltrates the BM
myelophthisic
2 main types of anemia of liver disease and characteristics
- chronic liver disease (target cells, acanthocytes from altered lipid metabolism)
- alcoholism (megaloblastic, hemolytic anemia)
