Anemia 2 Flashcards
causes for megaloblastic anemia
cobalamin (b12) or folate (b9) deficiency
important in purine synthesis -> dna synthesis
sources of cobalamin and folate
folic acid: uncooked green leafy vegetables
cobalamin: meat
causes of decreased intake of folate
poor nutrition old age, poverty, alcoholism hemodialysis premature infants spinal cord injury
causes of impaired absorption of folate
tropical and non-tropical sprue
other diseases of small intestine
causes of increased requirement for folate
pregnancy
chronic hemolytic anemia
exfoliative dermatitis
causes of impaired absorption of cobalamin
gastric
- pernicious anemia
- gastrectomy (intrinsic factor)
- zollinger ellison syndrome
intestinal causes
- ileal resection/disease
- blind loop syndrome
- fish tapeworm (d. latum)
causes of decreased intake of cobalamin
strict veganism
drugs that cause megaloblastic anemia
dihydrofolate reductase inhibitors in chemo
antimetabolites in chemo
inhibitors of deoxynucleotide synthesis
anticonvulsants
oral contraceptives
long term exposure to weak folate antagonists
smear findings in megaloblastic anemia
large red cells
large precursor cells in the marrow
neutrophils with hypersegmentation (only 3-5 segments)
treatment for megaloblastic anemia
oral or parenteral (for gastrectomy) cobalamin folate supplementation (green leafy vegetables, meat)
third most common cause of hypoproliferative anemia
anemia of inflammation or chronic disease
type of anemia in inflammation or chronic disease
normocytic normochromic anemia
normal to high (reactant) ferritin
low serum iron!!
pathophysio of anemia of inflammation or chronic disease
monocytes and t-cells are activated -> secrete ifn-y, tnf-a, interleukins -> inhibit release of epo + inhibit proliferation in marrow + increase hepatic synthesis of hepcidin -> iron is not released from stores and cannot absorb iron from gi tract -> low serum iron
augmented hemophagocytosis = eat more red cells
other effects of cytokine release
il1 = dec epo production tnf = suppresses epo response
== INCREASE LIVER SYNTHESIS OF HEPCIDIN
treatment of anemia of inflammation or chronic disease
treat underlying disease
epo or exogenous epo
characteristics of iron deficiency
mild to severe anemia microcytic hypochromic low serum iron low serum ferritin high tibc
characteristics of inflammation anemia
mild normocytic, normochromic low serum iron!! normal to high serum ferritin normal to low tibc
characteristics of renal disease
mild to severe anemia
normocytic normochromic
no epo production
presentation of aplastic anemia
hypoproliferative anemia = pancytopenia
decreased proliferation of ALL cell lines, not just rbcs
immune mediated t-cell destruction
common cause of aplastic anemia
idiopathic
drugs that cause aplastic anemia
benzene chloraphenicol chemo drugs nsaids anticonvulsants
viruses that cause aplastic anemia
hepatitis
hiv
parvovirus
ebv
other acquired causes of aplastic anemia
radiation
immune diseases
paroxysmal nocturnal hemoglobinuria
pregnancy
inherited causes of aplastic anemia
fanconi anemia
dyskeratosis congenita
schwachman-diamond syndrome
histology of aplastic anemia
devoid of hematopoietic elements
dominated by fat spaces
moderately severe aplastic anemia
hg <100 g/L
reticulocyte < 40 x 10^9/L
neutrophil <1.5 x 10^9/L
platelet <50 x 10^9/L
severe aplastic anemia
hg < 90 g/L
reticulocyte < 30 x 10^9/L
neutrophil <0.5 x 10^9/L
platelet <30 x 10^9/L
very severe aplastic anemia
hg <80 g/L
reticulocyte <20 x 10^9/L
neutrophil <0.2 x 10^9/L
platelet <20 x 10^9/L
treatment of aplastic anemia
hematopoietic stem cell transplantation = BEST TREATMENT
supportive treatment:
- red cell or platelet transfusion
- immunomodulatory agents (anti-thymocyte globulins, cyclosporine)
triad of paroxysmal nocturnal hemoglobinuria
pancytopenia
intravascular hemolysis
venous thrombosis
pathophysio of pnh
loss of phosphatidyl inositol glycan = loss of cd55 and cd59 = hemolysis
diagnosis of pnh
fluorescent aerolysin toxin (flaer)
ham’s test or acidified serum lysis test
treatment of pnh
hematopoietic stem cell transplant (have pig = cd55 and cd59)
eculizumab (prevents complement mediated hemolysis)
low dose steroids
supportive transfusions
features of hemolytic anemia
jaundice, pallor splenomegaly frontal bossing (congenital) low hemoglobin increased mcv and mch increased unconjugated bilirubin increased lactate dehydrogenase (high cell turnover) reduced to absent haptoglobin
classificaiton of hemolytic anemias
figure 9
inherited hemolytic anemias
hereditary spherocytosis (ankirin or spectrin deficiency, high mchc) hereditary elliptocytosis (membrane defect)
diagnosis of inherited hemolytic anemias
cbc
morphology
osmotic fragility test
treatment of inherited hemolytic anemias
supportive transfusion
splenectomy and gallbladder removal
___ is used in the hexose monophosphate shunt
glucose 6 phosphate dehydrogenase
purpose of hmp shunt
production of 5 carbon sugars in dna synthesis (deoxyribose and ribose)
only pathway to produce nadph
nadph is used in glutathione production to neutralize free radicals
treatment of g6pd deficiency
avoidance of oxidative stressors (e.g. fava beans)
avoid certain drugs
drugs that risk critical hemolysis
antimalarials
- primarquine, dapsone, chlorproguanil
- chloroquine
sulfonamides/suphones
- sulfamethoxazole, dapsone
antibiotics
- cotri
- nadilixic acid
- nitrofurantoin
- niridazole
antipyretics/analgesics
- acetanilide
- phenazopyridine
others: naphthalene, methylene blue, rasburicase
patho in autoimmune hemolytic anemia
red cell is coated with autoantibody due to failure of immune tolerance or autoimmune mechanisms = destroyed by macrophages
diagnosis of aiha
coombs test = coagulation of red cells
treatment of aiha
immunosuppression
- steroids
-rituximab: anti cd20 antibody
kills b cells that produce antibodies
