RBC and Bleeding Disorders IV Flashcards
PIGA mutation
in paroxysmal nocturnal hemoglobinuria
phosphatidylinositol glycan complementation group A gene
x-linked
paroxysmal nocturnal hemoglobinuria
mutation in PIGA
-rare
only hemolytic anemia caused by acquired genetic defect**
RBCs deficient in three GPI-linked proteins that regulate complement activity
-susceptible to lysis - intravascular hemolysis (MAC complex)
PNH at night
because blood pH slight decrease - increased activity of complement
death in PNH
venous thrombosis
-of hepatic, portal, or cerebral veins
progression of PNH
may go to AML or MDS
diagnosis of PNH
flow cytometry
-detects RBCs deficienct in CD59 and CD55
CD59
deficient in PNH
-detected with flow cytometry
tx of PNH
monoclonal antibody
- eculizumab
- inhibits conversion of C5
immunohemolytic anemias
Abs bind RBCs leading to premature destruction
aka autoimmune hemolytic anemias
warm Ab type
IgG antibodies active at 37C
primary
secondary, SLE, drugs, neoplasms
cold agglutinin type
IgM antibodies active below 37C
acute - mycoplasm infection, mono
chronic - idiopathic, neoplasms
cold hemolysin type
IgG antibodies active below 37C
rare - children with viral infections
children with viral infections
cold hemolysin type
mycoplasm and mono infection
cold agglutinin type
PCN and cephalosporin
drug induced warm-antibody type
alpha-methyldopa
telomerase breaking drug
lead to warm -AB type
paroxysmal cold hemoglobinuria
cold hemolysin type
IgG bunds P blood group antigens
mycoplasma pneumonia
cold agglutinin type of immunohemolytic anemias
IgM Abs bind RBC at low temperatures
direct coombs antiglobulin test
patient RBCs mixed with sera with Abs for Ig/complement
clumping
indirect coombs antiglobulin test
patients serum tested for ability to agglutinate commercial RBCs
test used to characterize antigen target and temperature dependence of responsible antibody
quantitative test**
to characterize antigen target and temperature dependence of responsible antibody
indirect coombs test
cardiac valve prosthesis
hemolytic anemia from RBC trauma
microangiopathic hemolytic anemia
seen with DIC, TTP, HUS, malignant HTN, and SLE, and disseminated cancers
microvascular lesion - luminal narrowing
deposition of fibrin and platelets
shear stress
schistocytes, burr cells, helmet cells, triangle cells
in PBS with traumatic hemolytic anemia
anemias with diminished erythropoiesis
nutritional deficiency, renal failure, chronic inflammation
less commonly bone marrow failure, aplastic anemia, neoplasm
extrinsic causes of diminished erythropoiesis
more common and clinically important
nutritional deficiencies
animal products
B12 higher
B12 and folic acid
coenzymes for synthesis of thymidine - DNA base
deficiency - megaloblastic anemia
intrinsic factor
binds B12 in stomach
haptocorrin
binds B12 in saliva
megaloblastic
impaired DNA synthesis
pernicious anemia
decreased B12
-autoimmune gastritis impairs IF production
cobalamin
B12
cubillin
receptor for IF:B12 aborption in ileum
hypersegmented PMNs
in megaloblastic anemia
also see giant metamyelocytes and band forms
parietal cells
produce intrinsic factor
spastic paresis, sensory ataxia, severe parathesias of lower limbs
neuro complications of B12 deficiency
autoimmune gastritis impairing production of IG
pernicious anemia
pernicious anemia clinical
scandinavian and other caucasian populations
disease of older adults
rare younger than 30
dx of pernicious anemia
1 moderate megaloblastic anemia
2 leukopenia with hypersegmented granulocytes
3 low serum B12
4 elevated homocysteine and methylmalonic acid
after tx with B12 in pernicious anemia
reticulocytosis and rising Hct 5 days after tx
pernicious anemia pathology
autoantibodies diagnostic utility - not primary cause
thought to be an autoreactive T-cell response*** - initiates gastric mucosal injury
type I pernicious anemia
block B12-IF binding
type II pernicious anemia
block IF:B12 to ileal receptor binding
type III pernicious anemia
85-90%
recognize alpha and beta subunits of gastric H+ pumps
