Hemolytic Anemia

• NC/NC

• polychromasia

what is the classification of hemolytic anemia?

shortened survival time

why is polychromasia present in hemolytic anemia?

• shortened red cell survival

• severity is dependent on:

  • degree of hemolysis

  • bone marrow erythroid compensatory response

what is a hemolytic state?

intracellular; defect of the cell

what is intrinsic hemolytic anemia?

extracellular; defect outside the cell

what is extrinsic hemolytic anemia?

substance in the plasma or condition affecting the circulatory sytem

what usually causes a defect outside the cell?

• abnormalities of the RBC membrane

• defective enzymatic pathways

• defective hemoglobin molecule

what are some examples of intrinsic hemolytic anemia?

• malaria parasitic infection

• antibodies to a RBC antigen

what are some examples of extracellular hemolytic anemia?

• rapid onset, sudden

• episodic

what characterizes acute hemolytic anemia?

• paroxymal nocturnal hemoglobinuria

• hemolytic transfusion reaction

what are some examples of acute hemolytic anemia?

• occurs over time

• may not be evident if the bone marrow can compensate, but may be punctuated over time with hemolytic crises

what characterizes chronic hemolytic anemia?

G6PD deficiency

what is an example of chronic hemolytic anemia?

• passed to offspring by parents

• due to a mutant gene

what characterizes inherited hemolytic anemia?

develop in individuals who were previously normal but occurs after exposure to a chemical/agent/condition

what characterizes acquired hemolytic anemia?

inherited

what are most intrinsic defects?

acquired

what are most extrinsic defects?

Paroxysmal Nocturnal Hemoglobinuria

what is the exception to intrinsic defects being inherited?

cell is destroyed in the vessel

what does intravascular mean?

• fragmentation

• complement is activated and destroys the RBC

how is intravascular hemolysis carried out?

cell is destroyed by the spleen

what does extravascular mean?

• macrophage-mediated

• cell is unable to escape the macrophage

how is extravascular hemolysis carried out?

90%

what percent of normal red cell destruction is extravascular?

10%

what percent of normal red cell destruction is intravascular?

polypeptide and iron

what components of hemoglobin catabolism are reused?

• bone marrow is capable of increasing output six-to-eight-fold

• little/no anemia

how is compensated bone marrow response characterized?

• bone marrow can no longer keep up

• red cell lifespan is usually only 15-20 days by this time

  • anemia is present

• may run out of iron/folic acid

how is uncompensated bone marrow response characterized?

• red cell membrane defects

• enzyme defects

• hemoglobinopathies

• thalassemia

what are the intracellular hereditary defects?

paroxysmal nocturnal hemoglobinuria

what is the acquired intracellular defect?

• immune hemolytic anemia

• infections

• chemicals and toxins

• physical agents

• microangiopathic hemolytic anemia

• hypersplenism

• general systemic disorders

what are the extracellular defects?

• hereditary spherocytosis

• hereditary elloptocytosis

• acanthocytosis

• stomatocytes

what are the membrane defects?

defective membrane skeleton of red cell

what characterizes hereditary spherocytosis?

defects in proteins that disrupt the vertical interactions between transmembrane proteins and cytoskeleton proteins

what causes a defective membrane skeleton in hereditary spherocytosis?

autosomal dominant

what type of inheritance is hereditary spherocytosis and hereditary elliptocytosis?

• ankyrin

• spectrin

what proteins are involved in the membrane skeleton of red cells?

destabilization of the lipid bilayer allowing lipids to escape

what does a defective membrane of red cells result in?

loss of surface area, resulting in decreased surface-to-volume ratio

what happens as a result of destabilization of the lipid bilayer?

cell loses its ability to deform

why is the survival time of RBC decreased when the lipid bilayer is destabilized?

• mild jaundice

• anemia

• enlarged spleen

what are clinical symptoms of hereditary spherocytosis?

elevated MCHC

what is the hallmark laboratory finding for hereditary spherocytosis?

• MCV~ normal/slightly decreased

• MCH~ elevated

• MCHC~ elevated, >36%

  • hyperchromic

• spherocytes on peripheral blood

• reticulocytosis

• increased chemistry results

  • LD is increased

  • Bilirubin is increased

• osmotic fragility is increased

• increased autohemolysis

what are the laboratory findings of hereditary spherocytosis?

• measures surface-to-volume ratio of RBC

• cells are placed in graded hypotonic salt solutions

• water enters cells, cell swells and bursts

what are characteristics of osmotic fragility?

less than normal cells

how do RBCs swell in hereditary spherocytosis?

higher concentration of salt than normal cells

how do RBCs lyse in hereditary spherocytosis?

0.45% NaCl

when does hemolysis begin in normal RBCs?

0.35-0.30% NaCl

when does 100% hemolysis occur in normal RBCs?

0.65% NaCl

when does hemolysis begin with hereditary spherocytosis?

spelectomy

how is hereditary spherocytosis treated in severe cases?

folic acid

how are children treated for hereditary spherocytosis if too young for splenectomy?

6

what age can children get splenectomy to treat hereditary spherocytosis?

0.5-2.5%

what is the normal range of reticulocytes?

bone marrow response to hemolysis

what do reticulocytes indicate in hereditary spherocytosis?

hereditary membrane defect

what is hereditary elliptocytosis?

different spectrin defect

what compromises the stability of cell membrane in hereditary elliptocytosis?

horizontal bonds on the skeleton causing ellipto-shaped red cells

what does hereditary elliptocytosis involve in the cell membrane?

most cells are elliptocytes

how does a peripheral blood smear of hereditary elliptocytosis appear?

• number of elliptocytes

• family history

what is the diagnosis of hereditary elliptocytosis based on?

• normal MCV

• normal MCH

• normal MCHC

• normal osmotic fragility

• normal autohemolysis

what are the laboratory findings of hereditary elliptocytosis?

• mild form needs no treatment

• more severe may require splenectomy

what is the treatment for elliptocytosis?

imbalance of cations

what causes stomatocytes?

• acute alcoholism

• malignancy

• medications

what are some examples of stomatocytes being commonly acquired?

dehydrated hereditary stomatocytes

what is the rare hereditary condition involving stomatocytes?

defect in cell membrane that allows permeability of potassium, but not sodium, causing loss of water from cell

what is Dehydrated Hereditary Stomatocytes?

inherited

what is pyropoikilocytosis usually?

• very abnormal shapes

• fragmentation

• microspherocytosis

• elliptocytosis

• RBCs show marked thermal sensitivity

what are the characteristics of pytopoikilocytosis?

after incubation of HPP cells at 41℃ to 45℃, the RBC fragments

how are HPP cells sensitive to temperature?

49℃

what temperature do normal RBCs fragment?

imbalance of cholesterol and phospholipid

how do acanthocyte membranes have an altered lipid content?

normal lifespan

what is the lifespan of cells in mild forms of acanthocytosis?

• liver disease

• congenital abetalipoproteinemia

what are acanthocytes observed in?

cup-shaped

what is the shape of stomatocytes?

reversible

what type of condition are stomatocytes?

slit-shaped/rectangular

what is the shape of the central pallor of stomatocytes?

• electrolyte imbalance

• liver disease

• artifact

what are stomatocytes observed in?

artifact

what is the most common cause of stomatocytes?

hereditary enzyme deficiencies

what is a cause of intracellular, extravascular hemolysis?

G6PD

what is the most common cause of hereditary enzyme deficiencies?

pentose phosphate/hexose monophosphate pathway

where is G6PD used?

glucose-6-phosphate dehydrogenase

what does G6PD stand for?

sex-lined, mutant gene

what transmits G6PD deficiency?

males

who is G6PD deficiency more common in?

the first step of the pentose phosphate pathway

when is G6PD catalyzed?

gluthathione is reduced

what happens when NADP is converted to NADPH?

protects hemoglobin from oxidative denaturation

what is the function of gluatathione?

• no NADPH

• reduced glutathione

• hemoglobin aggregates or precipitates

• premature destruction of red cells

what happens when there is a deficiency of G6PD?

when hemoglobin aggregates/precipitates

how are heinz bodies produced?

African American males and Asians

who is G6PD a relative common disorder in?

bone marrow compensates

why do most people never suffer any clinical manifestations during G6PD deficiency?

oxidative stress

what can lead to mild/severe hemolytic episode of G6PD deficiency?

fava bean

what sensitivity does oxidative stress with G6PD deficiency cause?

young erythrocytes

what cell is G6PD the highest?

sufficient NADPH; no glutathione

what do G6PD-deficient cells fail to produce?

oxidation of hemoglobin

what leads to precipitation in G6PD deficiency?

extravascular

what type of hemolysis occurs in G6PD deficiency?

• stress

• 2-3 days later, red cell count decreases

• anemia is NC/NC

• increased reticulocyte count

• Heinz bodies are present

what are the clinical manifestations of G6PD deficiency?

• G6PD activity decreases with cell aging

• young cells would falsely indicate a normal G6PD result

why is diagnosing G6PD deficiency difficult?

after crisis

when should G6PD testing be done?

• fluorescent spot test

• anticoagulated blood incubated with Glucose-6-phosphate/NADP reagent

• patient sample provides the G6PD enzyme to convert NAP to NAPH

what is the qualitative G6PD test?

pyruvate kinase

what is the second most common deficiency?

Embden-Meyerhoff pathway

what is pyruvate kinase involved in?

90%

what percent of cellular energy does pyruvate kinase provide?