Red Cell Disorders 3 Flashcards
what is the normal function of the PIGA gene?
synthesizes GPI anchor which is important for the anchoring of cell surface proteins on hematpoeitic cells
what are the CNS symptoms seen with B12 deficiency?
- paraparesis, sensory ataxia and lower limb paraesthesia
- degeneration of the dorsal and lateral tracts of the CNS
_____ is the most common cause of B12 deficiency
pernicious anemia
_______ hemolysis is seen with warm antibody immunohemolytic anemia
extravascular; antibody coated RBC’s are removed from circulation by phagocytes in the spleen
removal of ______ (part of the GIT) will make them at risk for B12 deficiency
terminal ileum
↑ or ↓ reticulocyte count seen in megaloblastic anemia
↓
describe the steps of B12 absorption from the diet
- haptocorrin binds to B12 and creates a complex
- pacreatic proteases in the duodenum releases B12 from the complex
- free B12 binds go intrinsic factor released by gastric parietal cells
- B12 is transported in the blood with transcobalamin
↑ serum methymalonic acid is seen in ______ deficiency
B12 (not seen in folate deficiency)
cold hemolysin involves ____ autoantibodies
IgG
most antibodies in warm antibody immunohemolytic anemia are _____ class
IgG
________ are at risk for B12 deficiency
vegans
______ tetramers are seen in fetus’s with hydrops fetalis
gamma
B12 is ultimately absorbed in the _______
distal ileum
_______ is a clinical presentation of someone with cold agglutinin type of antibody immunohemoltic anemia
Raynaud’s phenomenon: blue fingers
in the cold agglutinin type of cold antibody immunohemolytic anemia , there are ______ antibodies
IgM antibodies that react strongly at lower temperatures and not at normal body temperatures
what are the types of α thalassemia seen based on the number of genes deleted
- silent carrier : 1 α gene is only deleted
- minor: 2 α genes deleted
- HbH disease: 3 α genes deleted
- Hb Barts/ hydrops fetalis: all 4 α genes deleted
what are the three most important GPI linked proteins which are affected in someone with PNH
- decay accelerating factor (CD55)
- membrane inhibitor of reactive lysis (CD59)
- C8 binding protein
protect the cell from being destroyed by complement (intravascular hemolysis)
the more dangerous form of α thalassemia minor is seen in _____ populations
Asian: α / α, -/-
describe the pathogenesis of extravascular hemolysis seen in cold agglutinin type
- as the blood recirculates and warms IgM is released before the complement mediated hemolysis occurs but the IgM deposits C3b (an opsonin) leading to extravascular hemolysis
B cell lymphoma is associated with ____ antibody immunohemolytic anemia
warm and cold
PNH is due to mutations in _____ gene
PIGA gene (phosphatidylinositol glycan class A) which synthesizes GPI anchor which links many cell surface proteins to plasma membrane on hematopoietic cells X linked
nuclear/cytoplasmic asynchrony is see in _______ anemia
megaloblastic anemia because DNA synthesis is ↓ but normal RNA and protein synthesis
What are some general cause of impaired RBC production
- failure of proliferation and/maturation of committed RBC precursors such as DNA synthesis, heme synthesis, globin synthesis
- failure of stem cells: aplastic anemia
- unknown/multiple mechanism: anemia of chronic disease
why is there ↑ hemolysis during the night for PNH ?
- during the night, the ↓ of blood pH will ↑ the activity of complement leading to more hemolysis
what are some non immune hemolytic causes of anemia
- mechanical RBC damage: DIC, malignant HTN, TTP/HUS, SLE and disseminated dance r
- infections: malaria
the most common cause of death in patients with PNH is ______
thrombosis
what is the difference between the direct and indirect Coombs test?
- direct: tests for the antibodies or complements on the surface of the RBC
- indirect: detection of antibodies in the patient’s serum
cold agglutinins are produced in response to:
infections: mycoplasma, EBV, HIV, CMV, influenza
neoplastic growth: B cell lymphomas
what drugs will increase the chance of developing folate deficiency?
methotrexate and trimethoprim
cold agglutinin/hemolysin type is associated with intravascular hemolysis
- hemolysis (involves IgG)
agglutinin type involves IgM and will see extravascular hemolysis
__________ form of autoimmune hemolytic anemia is usually seen following viral infections in children
cold hemolysin type
absence of ____ and _____ would be seen on flow cytometry in someone with PNH
CD55 and CD59
what is the composition of hemoglobin H?
tetramer of β globin chains (due to excess β globin chains)
what are some associated conditions with PNH?
- thrombosis
- aplastic anemia
- iron deficiency
- AML and MDS (myeloid dysplastic syndrome)
folate is absorbed in the ______
proximal jejunum
______ is the only hemolytic anemia caused by an acquired genetic defect
paroxysmal nocturnal hemoglobinuria
What is the best method to diagnose PNH and what would you look for?
- flow cytometry in which you will see an absence of CD55 and CD59 on blood cells
beefy tongue is associated with _____
B12 deficiency due to megaloblastic changes in the oropharyngeal epithelium
pernicious anemia is an autoimmune disease where there is destruction of _____-
gastric parietal cells
hyperhsegmented neutrophils are seen in _____ anemia
megaloblastic anemia
