section 17 - anemias pt 2 Flashcards
define hemoglobinemia
excess hemoglobin in blood plasma
define hemoglobinuria
excess hemoglobin in urine
define hematuria
blood in urine
define hemosiderinuria
hemosiderin in urine
define the membrane defect in hereditary spherocytosis
- vertical spektrin ankyrin defect
- causes lipid destabilization and loss of membrane material with age
describe osmotic fragility with hereditary spherocytosis
increased
describe relative anemia (hydremia)
- increase plasma vol but stable hct
list possible causes of hydremia
- pregnancy
- hyperproteinemia
- mass IV or FFP infusion
describe classic presentation of hereditary spherocytosis
- jaundice
- splenomegaly
- anemia
describe treatment possibilities of HS
- if mod to severe hemolysis = splenectomy
- splenectomy will resolve symptoms but defect persists
lab findings of spherocytosis
- DAT (=)
- folic acid: decrease (using more)
- MCV: decrease
- MCHC: increased
- reticulocytes: increased in normal response
- RDW: increased
- osmotic fragility: increased
describe the principle of osmotic fragility
RBCs placed in hypotonic soln will draw in water and swell until lysis
at what point do normal rbc pops begin lysis
0.45% and complete at 0.35%
what is the osmotic fragility of target cells
decreased due to less hgb present opening up space for water
equation of osmotic fragility
% hemolysis = (OD of sample supernatant/OD of water tube)*100
at what point do spherocytes begin hemolysis in osmotic fragility testing
0.85%-0.55%
describe the main defect in hereditary elliptocytosis
defect in alpha or beta chain spectrin - horizontal interactions causing failure to return to disk shape
lab findings of hereditary elliptocytosis
- inc elliptocytes
- MCV norm-inc
- MCHC norm
- osmotic fragility norm
- may be mildly heat sensitive
what is the RBC morphology of spherocytic HE
spoon shaped ovalocytes
- protective against malaria
describe the defect of hereditary pyropoikilocytosis
alpha or beta spectrin mutation and decreased synthesis of alpha spectrin leading to fragmentation
describe thermal instability of hereditary elliptocytosis
- heated at 45 C they fragment
- normal cells fragment at 49C
findings of hereditary pyropoik
- facial bone abnormalities
- MCV decrease
- MCHC inc
- inc spherocytes/elliptocytes
- micro poik
describe defect of hereditary stomatocytosis
- deficiency of stomatin and failure of sodium potassium pump
- increase cellular water = cells swell
other lab findings of hereditary stomatocytosis
- MCV inc
- MCHC decrease
- stomatocytes
- osmotic fragility inc
- 2,3-BPG decrease
describe defect of hereditary xerocytosis
- cells lose potassium due to permeability defect causing dehydration
lab findings of hereditary xerocytosis
- MCV inc
- MCHC inc
- stomatocytes
- target cells
- puddle cells
- 2,3-BPG decrease
- osmotic fragility decrease
describe the defect in acanthocytosis
- abnormal membrane lipids reflect dist of plasma phospholipids
- acanthocytes contain excess cholesterol
describe possible causes of acanthocytosis
- hereditary absent LDL
- liver disease
- malnutrition
- certain blood groups
- vitamin E deficiency
generally describe anemia of liver disease
- cholesterol and lipids are inc leading to alteration of RBC
- round macrocytes
generally describe anemia of alcoholism
- ethanol has direct toxic effect on precursor cells, marrow cellularity, and rbc morphology
what is the most common hereditary enzyme deficiency
G-6-PD (X linked)
what is G6PD responsible for
- hexose monophosphate shunt and generation of NADPH to protect from oxidative injury
what are the consequences of oxidative agent activity
denatured hgb (heinz bodies) and skeletal structural abnormalities
how does G6PD result in hemolysis
- due to heinz body formation and removal
- limited to older cells due to lower amt of G6PD
- amt retics affect rate of hemolysis
what stain is used for identification of heinz bodies
supravital stains
how does the G6PD screening test determine G6PD deficiency
- G6PD deficiency shows no fluorescence under UV light
- cells with G6PD will fluoresce
what pathway is pyruvate kinase associated with
embden-meyerhof - ATP production
how does PK screening show deficiency
- PK deficiency shows fluorescence under UV light
how can PK deficiency be treated
it can’t, only supportive therapy
describe the defect in PNH
an acquired myeloproliferative disorder w/ defect in pluripotent stem cell causing absence of anchor protein
in PNH how does a lack of anchor protein affect the cell
no production of CD55 or 59 allowing complement fixation on the cell membrane
how does night time effect PNH
slow metabolic rate at night lowers plasma pH increasing complement activity and lysis
what can PNH evolve into
- aplastic anemia
- IDA
- 30% of patients have aplasia before PNH
describe the hemolytic factor of MAHA
RBC pass through fibrin strands and fragment
- chronic course
- DIC is an acute MAHA
what two disorders are associated with MAHA
- thrombotic thrombocytopenic purpura (TTP)
- hemolytic uremic syndrome (HUS)
define TTP
abnormal clots with low platelets and bruising
what is the mechanism causing TTP
- small platelet aggregates and unusually large vonWilebrand factor platelets swarm around
what causes long vonWillebrand factor
absent ADAMTS13
- responsible for cleavage of VW
how does vonwilebrand usually work in the body
- broken up pieces via ADAMTS13 are involved in adhesion of platelets to site of injury
what are the two forms of TTP
- acquired (more common): autoantibody to ADAMTS13
- rare inherited ADAMTS13 deficiency
describe HUS
- resembles TTP
- found in young children
- causes acute renal failure
- absence of neurologic symptoms
how does HUS associated with MAHA relate to infections
- after enteric infection toxins target renal capillary endothelium
- initiate DIC and cancels fibrinolysis
- platelet activation
- platelet aggregation in kidney
other causes of non-immune hemolytic anemia
- malignant hypertension
- DIC
- malignant fibrin
- chemotherapy
- aortic heart valve (unnatural tissue damages RBCs as they pass)
- march hemoglobinuria (physical damage)
describe autoimmune hemolytic anemia and two main kinds
Ab against self
- warm reactive (most common): IgG reacts at body temp, DAT +
- cold reactive: IgM reacts at 4C, DAT =
describe cold agglutinin disease syndrome
- anti-I, secondary to infection
- cold weather causes agglutination of RBC in skin capillaries
- DAT + at 15-32 for complement
describe paroxysmal cold hemoglobinuria (PCH)
- common in kids
- associated with viral disorder
- IgG binds and fixes complement at low temp
- hemolysis of fixed cells at higher temps
what is the classid antibody of PCH
donath-landsteiner
describe immune complex drug induced hemolytic anemia
drug and pt Ab form complex that attaches RBC and activates complement
describe hapten drug induced hemolytic anemia
drug nonspecifically bound to RBC and pt develops anti-drug Ab that reacts with cell bound drug
define alloimmune hemolytic anemia
antibody against foreign antigen - typically transfusion rxn or HDN
describe the principle kleihauer betke test for fetal hgb detection
all hgb elute from rbcs in acid bath, hgb F elutes slower and can be distinguished from adult hgb once stained with hgb stain
