B3.047 Hypoproliferative Anemia Flashcards
what is the best way to differentiate between inadequate and ineffective production from BM?
look at a bone marrow aspirate
full- ineffective
empty- inadequate
what are some potential causes of inadequate BM production?
bone marrow failure
bone marrow infiltration/ replacement (myelophthisis)
nutritional deficiency
anemia of chronic disease
what are some reasons for bone marrow failure? which is most common?
aplastic anemia
pure red cell aplasia
iatrogenic - most common, many immunosuppressive meds
what are some ways that ineffective production in the BM manifests?
cells collect in BM and don’t leave
OR
rapid destruction within the BM
what is aplastic anemia?
myeloid stem cell disorder
marrow hypoplasia and pancytopenia
aplastic anemia epidemiology
incidence - 2-5 cases / 1,000,000 per year
clinical features of aplastic anemia
anemia
leukopenia
thrombocytopenia
no splenomegaly
why is aplastic anemia a misnomer?
hypoplastic, not completely aplastic
all myeloid cell lines, not just RBCs
pathogenesis of aplastic anemia
primary stem cell abnormality
OR
immune mediated stem cell destruction
immunological factors causing aplastic anemia
idiopathic
viral infections
environmental factors causing aplastic anemia
drugs/chemicals
whole body radiation
viral infections
genetic factors causing aplastic anemia
Fanconi
telomerase defects
acquired stem cell defects
potential for acquisition of additional mutations and transformation into AML
aplastic anemia blood path
pancytopenia
normochromic, normocytic RBCs, no poikilocytes
reticulocytopenia
aplastic anemia BM path
hypocellular
decreases hematopoiesis
increased marrow fat
aplastic anemia treatment
supportive (transfusions)
immunosuppression (see if it works to differentiate between immunologic or clonal)
androgens
hematopoietic stem cell transplant
aplastic anemia prognosis
1 year without treatment
75% 5 year survival with transplant
50-70% response to immunosuppression
what is pure red cell aplasia
disorder or erythroid progenitor cell causing decreased erythropoiesis
epidemiology PRCA
very rare
clinical features of PRCA
anemia
pathogenesis of PRCA
thymoma (paraneoplastic syndrome)
viral infection (parvovirus B19)
drugs
autoimmune disorders
describe parovirus B19 and its relationship to PRCA
small minority of people affected get severe BM suppression
transient drop in Hgb that self recovers
people who have hemolytic anemia (need BM to always work well) can have severe aplastic crisis
PRCA blood path
normochromic, normocytic anemia
no poikilocytes
reticulocytopenia
PRCA bone marrow path
markedly decreased erythroid precurors
intranuclear inclusion in erythroblasts in parvovirus B19 infection
treatment of PRCA
thymectomy
plasmapheresis
androgens
supportive (transfusion)
prognosis of PRCA
median survival >10 y without treatment
50% spontaneous remission
50% cure rate with thymectomy
what is myelophthisic anemia?
decreased erythropoiesis due to bone marrow infiltration or replacement
clinical features of myelophthisic anemia
anemia
features of underlying disease
myelophthisic anemia pathogenesis
metastatic cancer
fibrosis (primary myelofibrosis or following treatment)
hematopoietic neoplasms
myelophthisic anemia blood path
normochromic, normocytic anemia teardrop shaped RBCs circulating nucleated RBCs granulocytic left shift reticulocytopenia
myelophthisic anemia BM path
replacement of normal elements
what is Plummer-Vinson syndrome (Paterson-Brown-Kelly syndrome)
iron def anemia
atrophic glossitis
esophageal webs
what is anemia of chronic disease associated with?
systemic inflammation
chronic infection
autoimmune disorders
cancer
pathogenesis of anemia of chronic disease
decreased proliferation of RBC precursors
impaired iron utilization
-increased hepcidin due to inflamm mediators like IL-6
-decreased transfer of iron to RBC precursors in BM
pathology of anemia of chronic disease
microcytic or normocytic anemia minimal anisocytosis no increase in reticulocytes decreased serum iron normal or increased ferritin decrease or normal transferrin and soluble transferrin receptor increase storage iron in BM
what is megaloblastic anemia?
macrocytic anemia due to def of vitamin B12 or folic acid
impaired DNA synthesis due to defective thymidine synthesis
ineffective hematopoiesis
what is vitamin B12 used for?
regeneration of folate
what is folate used for?
synthesis of DNA from thymidine
run through the steps of vitamin B12 absorption
- B12 is bound to proteins in food and enters mouth
- gastric acid causes B12 to disassociate from binding protein in stomach
- B12 complexes with haptocorrin (made in salivary glands)
- proteases from the pancreas separate B12 from haptocorrin in the intestine
- B12 complexes with IF in ileum
- IF receptors allow B12 to be absorbed
- stored in liver
why is supplementing B12 into a diet/orally not always effective?
there could be a problem with any of the steps in the absorption process
need to five a shot
what are some reasons for vitamin B12 def
decreased intake- vegan diet impaired absorption -IF def -malabsorption -ileal resection -bacterial overgrowth in blind loops -fish tapeworm infection
what are some reasons for folic acid def
decreased intake (impaired diet, alcoholism) impaired absorption -malabsorption -intestinal disease -anticonvulsants, oral contraceptives increased loss increased requirement -pregnancy, infancy, disseminated cancer, markedly increased hematopoiesis impaired utilization -folic acid antagonists
clinical features of megaloblastic anemia
anemia
neurological deficits - with vitamin B12 def only
-demyelinatin of dorsal and lateral spinal tracts
-spastic paraparesis, sensory ataxia, severe parasthesia
pathology of megaloblastic anemia
macrocytic anemia- macroovalocytes
hypersegmented neutrophils
megaloblastic hematopietic precursors
pathology of vitamin B12 def
brain and spinal cord demyelination intrinsic factor antibodies in pernicious anemia low serum vitamin B12 high serum methylmalonic acid* high serum homocysteine* *precursors usually acted on by B12
pathology of folic acid def
low serum and RBC folate
high serum homocysteine
what would be the problem with treating B12 def with folic acid?
exacerbate neurological deficits despite improving anemia
