macrocytic anemias Flashcards
what is a macrocytic anemia
- retic are big
- grouped as megaloblastic vs macrocytic
- > 100 MCV vs > 115 MCV
mechanisms of macrocytic anemia
- abnorm in DNA metabolism (b12 or folate def)
- shift to immature cells
- bone marrow disorders- MDS
- hypothyroidism
- alcoholism
how does alcoholism cause macrocytic anemia
- unknown mechanism
- acetaldehyde has direct effect on RBCs
- d/t regular ingestion of 80 g of alcohol daily
- resolution after 2-4 mo
types of macrocytic anemias
- reticulocytosis
- alcoholism
- liver disease
- hypothyroidism
- med effect
- aplastic anemia
types of megaloblastic anemia
- B12 def
- folic acid def
meds that cause macrocytic anemias
- combo antiretroviral therapy for HIV
- hydroxyurea for sickle cell disease
- mtx- inhibits dihydrofolate reductase
aplastic anemia
- considered a macrocytic anemia
- more common in Asia
- biphasic age distribution: 10-25 vs > 60
causes of aplastic anemia
- acquired causes
- autoimmune
- congenital causes
- fanconi anemia
- dyskeratosis congential
acquired causes of aplastic anemia
- radiation and chemo, toxins
- viral infx
- drugs
- immune disorders
- pregnancy
clinical presentation of aplastic anemia
- weakness, fatigue
- cardiopulm compromise
- progressive anemia
- mucosal/ skin bleeding, petechiae, menorrhea in women
- recurrent infx
what is a common cause of death in aplastic anemia
- invasive fungal infections
PE findings for aplastic anemia
- generally not helpful
- pallor or petechiae common
- purpura
lab study findings in aplastic anemia
- pancytopenia, severe anemia
- normocytic or macrocytic
- decreased or absent polychromic RBCs
- reduced cell components, morphologically normal
- abnormal cells NOT present
- retic count decreased
diagnostic criteria for aplastic anemia
- bone marrow cellularity < 30%
- absence of severe pancytopenia
- depression of 2-3 blood elements below normal
severe aplastic anemia criteria
- bone marrow bx shows < 25%
- OR
- bone marrow bx showing< 50% with the following:
- < 30% of cells are hematopoietic
- absolute retic count < 40,000
- absolute neutrophil count < 500
- platelet count < 20,000
very severe aplastic anemia
- criteria for severe met
- ANC < 200
essentials for dx of aplastic anemia
- pancytopenia
- no abnormal hematopoietic cells in circulation or in bone marrow
- hypocellular bone marrow
treatment for mild-mod aplastic anemia
- supportive care, treat underlying cause
- EPO GF likely wont work
- myeloid GF
- transfusions
- abx or antifungals for infx
- monitor closely
treatment for severe aplastic anemia
- allogenic HSCT tx of choice in kids < 20, preferred in adults 20-50
- immunosuppressive if adults > 50 without HLA match, consider with severe comorbidities
prognosis of aplastic anemia
- if untreated 70% 1 year mortality
- rapidly fatal if severe and untreated
- most die from fungal infections
- good survival if HSCT, immunosupressives, improved supportive care
- 1/3 of pts will relapse
fanconi anemia
- most common cause of congenital inherited aplastic anemia
- autosomal recessive, dx very young d/t severe congenital abnorm
- progressive bone marrow failure
what is a complication of fanconi anemia
- increased malignancy like AML or ALL
treatment for fanconi anemia
- supportive modalities
- androgens
- hematopoietic GF for transient improvement
- many become refractory or dev intolerable side effects
- allogenic HSCT is only option to restore function
when would you consider a B12 or folate deficiency based on H&P
- unexplained neuro si/sx
- older adults
- alcoholics
- patients with malnutrition
- bariatric surgery pts
b12 absorption
- comes from animal products: meat, fish, dairy
- requires intrinsic factor to be absorbed
- B12 + intrinsic factor complex absorbed in terminal ileum
how long is B12 sotred for
- 3 years
what are the functions of B12
- nucleic acid metabolism
- myelin synthesis
- critical for DNA synthesis and regulation
causes of B12 deficiency
- dietary def is rare
- inadequate intrinsic factor
- pancreatic insuff
- ileal disease
- competition for B12 in gut
- meds that block absorption: PPIs, metformin
- transcobalamin II def- rare
si/sx of B12 def
- based on severity of def
- glossitis
- vague GI disturbances
- neurologic sx*
neuro sx assoc with B12 def
- peripheral nerves affected first- distal/ peripheral paresthesias
- difficulty with balance and proprioception
- altered cerebral function
PE findings for B12 def
- pale
- mildly icteric or sallow
- atrophic glossitis
- decreased vibration
- decreased proprioception
- memory disturbances
lab findings for B12 def
- macrocytic, MCV 110-140
- HCT as low as 10-15%
- pancytopenia if severe
- low retic count
- low serum b12
- elevated MMA*
- elevated total homocystein*
- elevated LHD and indirect bili
- consider TSH and liver fn
essentials of B12 def
- macrocytic anemia
- megaloblastic anemia
- low serum B12
treatment of B12 def
- parenteral replacement if absorption issues: SC or IM
- sublingual or PO replacement indef
- concurrent folic acid tx: 1 mg PO 1-4 mo
- transfusion rarely needed
expected response to B12 def tx
- immediate improval
- hematologic picture normalizes in 2 mo
- hypoK possible in first few days
- reticulocytosis days 5-7
- hypersegmented neutrophils disappear after 10-14 d
- neuro sx may persist if present for > 6 mo before tx
monitoring tx for B12 def
- CBC: 1-2 weeks, 2 mo, periodic
- B12 levels: indefinite monitoring
what is pernicious anemia
- autoimmune disease
- Ab destroy parietal cells -> atrophic gastritis, bind to/ neutralize intrinsic factor
- higher risk for GI/ gastric cancers
- must treat B12 def
diagnosis of pernicious anemia
- schilling test*
- measure gastric acid secretion
- Ab to intrinsic factor
- anti-parietal cell Ab
- serum gastrin elevated
- serum pepsinogen low
- ratio to pepsinogen I: pepsinogen II low
where is folic acid found
- fruits
- leafy greens
- folate= found in nature
- folic acid= synthetic version
daily requirements of folic acid
- healthy pts: 50-100 mcg/d
- pregnant/ lactating pts: 600-800 mcg/d
how long is folic acid stored in the body
- 2-3 moths
where is folic acid absorbed
- through entire GIT
- duodenum or jejunum
function of folic acid
- common pathway with B12
- nucleic acid metabolism
- critical in DNA synthesis- synth in hematopoietic cells
causes of folic acid def
- inadequate daily intake*- most common
- reduced absorption- rare
- increased requirement i.e. pregnancy
- excessive loss
- meds
- alcohol abuse- lower folic acid stores
medications that can cause folic acid def
- mtx
- trimethoprim
- ethanol
- phenytoin
si/sx of folic acid def
- based on severity of anemia
- glossitis
- vague GI disturbances
- NO neuro sx
PE findings for folic acid def
- depends on severity
- pale
- mildly icteric or sallow
- atrophic glossitis
- neuro exam normal*
lab findings for folic acid def
- macrocytic anemia- MCV 110-140
- pancytopenia if severe
- low retic count
- normal B12
- RBC folic acid level low
- elevated homocysteine*
- normal MMA*
- elevated LDH and indirect bili
- consider TSH and liver fn
essentials of folic acid def dx
- macrocytic anemia
- megaloblastic blood smear
- reduced folic acid levels in RBCs or serum
- normal B12 levels
treatment of folic acid def
- folic acid PO daily for 1-4 mo or until hematologic recovery
- continue tx if underlying cause cant be fixed
- ensure no B12 def
expected response to tx of folic acid def
- rapid improvement within 5-7 d
- reticulocytosis in 5-7 d
- normalization of hematologic abnormalities within 2 mo
