Normocytic-Normochromic Anemias Flashcards
What are the three types of N-N anemias?
Aplastic anemia
Hemoglobinopathies
Hemolytic anemias
What is an aplastic anemia?
disorder or group of disorders characterized by cellular depletion and fatty replacement of the bone marrow. The bone marrow stain is hypocellular and failing.
Name the most common, the four secondary, and the congenital cause of aplastic anemia.
Main - idiopathic
secondary - chemicals, drugs (chloramphenical), radiation, chronic infections
congential - Fanconi’s anemia
What are the clinical features and course for aplastic anemia?
Gradual onset but as pancytopenia worsens.. Decreased WBC -> infection Decreased RBC -> fatigue, pallor, SOB Decreased PLT -> bleeding, bruising Hypocellular BM Decreased to absent retics
What are the treatments for aplastic anemia?
Take away offending agent if possible. Support therapy including antibiotics, blood products, growth factors. Immunosuppressive therapy or a bone marrow transplant.
What is the most common poik found in almost every hemoglobinapathy?
sickle cells
What is the amino acid substitution found in sickle cell anemia?
On the beta chain at the sixth position, glutamic acid is replaced by valine
What should you think of when you see a N-N anemia with a predominance of target cells?
hemoglobinopathy and look for tell tale poik
Describe the pathophysiology of sickle cell anemia
Hypoxic state in tissues causes the HGB S molecule to realign and the RBCs take on a sickle shape. The more the small vessels get occluded the lower the pH gets. This causes more sickling and tissue damage causing painful crises and infarction of organs.
What are three factors that contribute to the sickling process?
Hypoxia, acidosis, and dehydration
Discuss the cause for Painful crises, acute chest syndrome, and high risk of infections in sickle cell anemia
Painful crises - tissue damage precipitated by infection, fever, dehydration, exposure to extreme cold
acute chest syndrome - is caused by infaction of organs like an autosplenectomy in which the spleen becomes nonfunctional
high risk of infections - when the spleen gets nonfunctional it cannot fight infections
Describe the reason and method of the sickledex solubility test
Blood is added to a reducing agent, sodium dithionite or sodium metabisulfite. if HGB S is present, it will precipitate out giving a turbid (+) solution.
This will not differentiate between sickle trait and disease.
What are causes for false pos and false neg on the solubility screening test?
False pos - proteinemia and > 18 g/dL HGB
False neg - testing a newborn (gamma to beta switch hasnt occured) or < 7 HGB or multiple transfusions
What is the expected results for HGB electrophoresis with sickle cell anemia?
S > F (no A)
What is the RBC morphology for sickle cell anemia?
Targets plus sickles schistos spheres
polychromasia, increased retics
inclusions H-J pappenheimer
nRBC
What are the differences in sickle cell trait compared to sickle cell anemia?
The trait is heterozygous (AS) rather than homozygous (SS)
Electrophoresis for the trait is A > S whereas A is nonexistant with sickle cell disease.
The trait will show no sickles on a smear unless under a severe hypoxic state
No significant clinical features or treatment.
What are the treatments for Sickle Cell Anemia?
Stay hydrated, pain relief for crises, antibiotics, blood transfusions hydroxyurea to increase HGB F, transplant
What is the amino acid substitution for HGB C disease?
Lysine substitution for glutamic acid
Compare and contrast HGB C disease and trait
HGB C disease is homozygous CC while the trait is heterozygous AC
The disease is mildly hemolytic with splenomegaly while the trait is asymptomatic
Electrophoresis - Disease = 100% C (no A)
Trait = A > C
The disease will have targets plus C crystals and polychromasia (increased retics)
The trait will only have targets
What is the inheritance pattern of SC disease?
its a double heterozygous syndrome in which one parent donates a lysine substitution (C) and another parent donates a valine substitution (S)
Clinically it is less severe than sickle cell disease but still a mild-mod sever hemolytic anemia with crises
What are the electrophoresis results and RBC morphology for SC disease? S = C
Targets plus sickles, C crystals, and S-C crystals, polychromasia/ increased retics, H-J, Pappenheimer, nRBC
What is the inheritance pattern of sickle cell-beta thalassemia?
double heterozygous syndrome
one valine substitution (S) from one parent and a Bo or B+ from the other
S/Bo will be a severe hemolytic anemia whereas S/B+ can be mild to moderate hemolytic
What is the hemoglobin electrophoresis results for S/Bo and S/B+
SBo - S > F(^) > A2(^) with no A
SB+ - S > A > F(^) > A2(^)
What is the RBC morphology for sickle cell beta thal?
Rule of 3 is affected, too many reds for the hemoglobin. Hypochromic-microcytic, targets plus sickles (usually) spheres, schistos, nRBC
What are two ways to differentiate HGB D from HGB S since they both migrate to the same point on cellulose acetate electrophoreses?
D migrates with S and G
the solubility test will be negative for HGB D
or run a citrate (acid) electrophoresis
this is also a non sickling hemoglobin
What is the worlds third most common abnormal HGB (besides S and C) and what geographic area does it commonly occur?
HGB E and SE asia
State the physiological mechanism for the predominant type of poik found in hereditary spherocytosis, elliptocytosis, and stomatocytosis
hereditary ellipto - a decrease in cholesterol in cell membrane causes hemoglobin to polarize to opposite ends forming elliptocytes
hereditary sphero- a decrease in spectrin causes an increased permeability of sodium into the cell and thus a loss of surface area to volume ratio
hereditary stomats - defect in sodium potassium pump results in abnormal slit like pallor
What are the CBC indices and RBC morphology for hereditary spherocytosis?
CBC
mild anemia (HGB ~ 12)
normal MCV
MCHC 36-38%
Morphology
poik - variable number of spheres
polychromasia and increased retics
Clinically seen with jaundice, anemia, and splenomegaly
What is the principle of the osmotic fragility test
Blood is added to a series of hypotonic salt solutions and the beginning and end of hemolysis is noted
Beginning (0.45-0.5% NaCl)
End (0.30-0.35% NaCl)
Which conditions show a “shift to the left”
the presence of spherocytes will cause a left shift because an INCREASE in osmotic fragility
also associated with a DECREASE in resistance to hemolysis
Which conditions show a ‘shift to the right’
Targets, hypochromia, SICKLES (greatest resistance)
(thalassemias)
there is a DECREASE in osmotic fragility and an INCREASE in resistance to hemolysis
What results do you expect to see with any hemolytic anemia ?
Plasma haptoglobin = decreased or absent
reticulocyte count = increased
serum bilirubin = increased
serum iron and ferritin = increased
What is the clinical result of a G-6-PD deficiency?
G-6-PD is needed in the hexose monophosphate shunt to protect HGB from oxidative denaturation
Marked decrease in RBC count (increased retics) hemoglobinuremia hematuria jaundice Heinz bodies and bite cells
What are the triggering factors in a G-6-PD deficiency?
Moth balls, fava beans, new drug, or infection
What is the result of a PK deficiency?
Needed for anaerobic pathway so results in a decreased ability to make ATP
mild to severe hemolytic disease
Burr cells
What is the result of a methemoglobin reductase deficiency?
results in increased levels of methemoglobin which cannot carry oxygen
generally benign since enough ‘normal’ HGB made
if severe, people can become cyanotic
What is the etiology and clinical presentation of PNH
Abnormality in hematopoietic stem cell membrane that probably resulted from a mutation
causes cells esp. RBCs to be more sensitive than normal to the lytic action of C’ in an acidic condition
the body becomes slightly acidic during sleep causing ‘sleep induced hemolytic anemia ‘
first urine is bloody and clears throughout the day
some patients can have remission while others enter a preleukemic state
What is the expected CBC and morphology of PNH
pancytopenia
no rbc morphology
What are the results of a Ham’s acid test with a PNH sample?
there will be a positive result because the serum is acidified which activates c’ and lyses PNH-sensitive RBC
What is the etiology for a cold agglutinin
results from an autoimmune IGM antibody
Clinically rare except in older patients
avoid cold seasons/temps
What is the CBC for a cold agglutinin
rbc, H&H dont match
decreased RBC count with a MCHC over 40
increased MCV
What antibody is associated with paroxysmal cold hemoglobinuria
Donath Landsteiner Antibody
List two disorders commonly assiciated with microaniopathic hemolytic anemia MAHA
hemolytic uremic syndrome and thrombocytopenic purpura
What is the predominant poik associated with MAHA
schistocytes
