Hypoproliferative Anemias Flashcards
reticulocyte index for hypo proliferative anemias
- below 2%
absolute retic count for hypoproliferative anemias
- below 75,000
definition of megaloblastic anemias
- group of disorders characterized by a defect in DNA synthesis leading to a characteristic morphology of bone marrow cells
most common causes of megaloblastic anemias
- B12
- folate deficiency
typical presenting feature of megaloblastic anemia
- anemia
hematologic presentation of megaloblastic anemia
- elevated MCV and RDW
peripheral smear of megaloblastic anemia shows
- hypersegmented PMNs (neutrophils)
non-hematologic presentation of megaloblastic anemia
- beefy red smooth tongue
- neuro/psychiatric features
beefy red smooth tongue seen with which deficiencies
- B12
- folate
neuro/psychiatric features seen with which deficiencies
- B12 only
if you are folate deficient, what precursor will build up?
- homocysteine
if you are B12 deficient, what precursor will build up
- homocysteine
- methylmalonic acid
homocysteine important for
- DNA synthesis
methylmalonic acid important for
- myelin synthesis
homocysteine path
- homocysteine
- methionine
- DNA synthesis
methylmalonic acid path
- methylmalonic acid
- succinic acid
- myelin synthesis
how does B12 get into the body
- diet
- animal products
parietal cells in stomach secrete
- intrinsic factor
what does B12 bind to
- salivary R protein in acidic environment
role of pancreatic enzymes
- degrade R protein
- frees B12
B12-IF complex taken up by cells in
- distal ileum
B12 carried in blood by ____ to ____
- transcobalamin
- tissues
causes of B12 deficiency
- inadequate dietary intake
- inadequate absorption
- reduced B12 absorption in ileum
- pancreatic insufficiency
- competition for B12
- inactivation of cobalamin
inadequate dietary intake - B12 deficiency
- vegan diet
- no animal products
inadequate absorption - B12 deficiency
- lack of gastric acids
- destruction or removal of parietal cells
- gastric bypass
destruction/removal of parietal cells by
- pernicious anemia
- gastrectomy
reduced B12 absorption in the ileum
- Crohn’s disease
- Sprue
- Metformin
Sprue
- celiac
- tropical
competition for B12
- fish tapeworm,
- bacterial overgrowth
what inactivates cobalamin
- nitrous oxide
neurologic changes of B12 deficiency
- loss of vibration and position sense - subacute degeneration of the spinal cord
- dementia “megaloblastic mania”
laboratory findings of B12 deficiency
- macrocytosis
- hypersegements PMNs
- pancytopenia
lab findings with severe B12 deficiency
- elevated bilirubin and LDH
- due to intramedullary hemolysis
diagnosing B12 deficiency
- low B12 level
- elevated homocysteine
- elevated methylmalonic acid
how long does B12 deficiency take to develop
- years
treat B12 deficiency
- treat underlying cause
- IM injection of B12 lifelong
folic acid is absorbed where
- through the small intestine
folate is found in what food products
- uncooked leafy green vegetables
- bread, cereal products
enterohepatic circulation important for
- folate absorption
biliary drainage causes
- profound folate deficiency that occurs within hours
extra folate should be given to these people
- patients with hemolytic anemias and psoriasis
- women contemplating pregnancy
- pregnant/lactating women
folate stores in liver for how long
- 2-5 months only
most common cause of folate deficiency
- malnutrition
why do we give folate to women contemplating pregnancy
- prevent neural tube defects
definition of aplastic anemia
- pancytopenia in peripheral blood w hypocellularity in marrow
pancytopenia
- decreased WBCs, RBCs, and platelets
bone marrow biopsy of aplastic anemia shows
- hypocellularity
- deficiency of hematopoietic stem cells
aplastic anemia can also be considered
- an autoimmune condition
secondary causes of aplastic anemia
- ionizing radiation
- cytotoxic chemotherapy
- benzene exposure
- viruses
- PNH
viruses associated with aplastic anemia
- EBV
- non Hep A, B, C, D, or E
anemia in aplastic anemia symptoms
- weakness
- fatigue
low platelets in aplastic anemia symptoms
- bruising
- oozing
low neutrophil counts in aplastic anemia symptoms
- infection fever
is there splenomegaly or adenopathy in aplastic anemia
- no!
making diagnosis of aplastic anemia
- rule out other causes of pancytopenia
- think about exposures to drugs, test for viruses
- test for PNH
- bone marrow biopsy
rule out other causes of pancytopenia
- B12/folate deficiency
- splenomegaly
- other marrow toxins such as alcohol
- autoimmune conditions such as lupus
what to look for in bone marrow biopsy
- degree of cellularity
- rule out cancer, infiltrative disorders
- rule out dysplasia
infiltrative disorders
- sarcoidosis
- fibrosis
dysplasia disorders
MDS
treatment of aplastic anemia
- supportive care
- definitive therapy
supportive care of aplastic anemia
- transfusions
- antibiotics
- growth factors
definitive care of aplastic anemia
- stem cell transplantation
- T cell directed immunosuppression with antithymocyte globulin (ATG) and cyclosporine
stem cell transplantation mostly used in
- younger patients
T cell directed immunosuppression with antithymocyte globulin (ATG) and cyclosporine mostly used in
- older patients
- those without donor match
paroxysmal nocturnal hemoglobinuria is what kind of disorder
- clonal hematologic disorder
abnormal clone for paroxysmal nocturnal hemoglobinuria is missing which gene
- PIG-A
purpose of PIG-A
- makes GPI
purpose of GPI
- anchors several proteins to cell surface
most important GPI proteins
- CD55
- CD59
function of CD55 and CD59
- inhibit complement on surface of red cells
PNH clinical manifestations
- hemolysis at night
- thrombosis
- bone marrow failure
hemolysis at night in paroxysmal nocturnal hemoglobinuria leads to
- free hemoglobin lost in urine
- leads to development of iron deficiency
types of thrombosis in paroxysmal nocturnal hemoglobinuria
- arterial and venous
think of paroxysmal nocturnal hemoglobinuria when you see
- Budd Chiari syndrome
Budd Chiari syndrome
- thrombosis of the hepatic veins
- leads to hepatic failure
PNH leads to predisposition of other diseases such as
- MDS
- AML
intravascular hemolysis leads to
- low nitric levels
- defect in smooth muscle relaxation
defects in smooth muscle relaxation
- esophageal spasm
- erectile dysfunction
- pulmonary hypertension
how to treat hemolysis in PNH
- a drug!
- eculizumab
MOA of eculizumab
- targets C5
- blocks terminal complement activation
eculizumab will increase susceptibility to infection with
- Neisseria organisms
most common form of inherited aplastic anemia
- Fanconi’s anemia
Fanconi’s anemia genetic linkage
- autosomal recessive
- X-linked
Fanconi’s anemia due to mutation in
- 1 of 16 genes for DNA repair
clinical manifestations of Fanconi’s
- pancytopenia with macrocytic anemia
- other somatic abnormalities
increased incidence of ____ in Fanconi”s
- AML
- solid tumors
Fanconi’s usually presents in
- early childhood
characteristic congenital mutations of Fanconi’s
- hypo-pigmented spots and cafe-au-lait macules
- abnormalities of thumbs and radii
diagnosis of Fanconi’s
- culture lymphocytes or fibroblasts with DEB (diepoxybutane)
- look for abnormal chromosomal breakage
treatment of Fanconi’s
- allogenic transplant
- not much chemotherapy and radiation
Dyskeratosis congenita inherited disorder of
- telomere shortening
- inherited form of aplastic anemia
Dyskeratosis congenita clinical characteristics
- bone marrow failure
- predisposition to AML and other solid tumors
classic triad of Dyskeratosis congenita
- mottled hyperpigmentation of skin involving arms, shoulders, neck, torso
- abnormal nails of fingers and toes
- mucosal leukoplakia - white lesions
additional findings in Dyskeratosis congenita
- pulmonary fibrosis
- prematurely gray hair
- cirrhosis of liver
treatment of Dyskeratosis congenita
- allogenic transplant with not much chemotherapy and radiation
differential diagnosis of hypoproliferative anemias
- acute blood loss or destruction
- nutritional anemia
- bone marrow depression
- defective RBC production
- destruction of erythroid precursors
- replacement of normal marrow
BAD DNR
nutrients necessary for normal erythropoesis
- iron
- B12
- folic acid
defective RBC production by
- kidney disease
- myelodysplasia
destruction of marrow erythroid precursors by
- aplastic anemia
- parvovirus infection
