Anemia Flashcards
What is anemia
Anemia is the lack of normally formed, properly functioning RBCs in the circulation, which impairs the body’s ability to oxygenate the tissues at optimal level.
Anemias may be qualitatively or quantitative or both. Meaning?
Quantitative: Decreased RBC count
Qualitative: Disordered cellular morphology or hemoglobin structure
How can you see RBC abnormalities
CBC, hemoglobin electrophoresis, peripheral blood smear, bone marrow aspirate (rarely and if necessary)
3 pathophysiologic mechanisms resulting in anemia
Underproduction of RBCs
Increased premature destruction of RBCs
Leakage out of circulation eg. in bleeding
Cases where we see impaired marrow production
substrate deficiency states: iron/folate deficiency
Disorders of heme synthesis: sideroblastic anemia
Disorders of hemoglobin synthesis: Thalassemias
Impaired marrow responsiveness to erythropoietin: anemia of chronic disease
Bone marrow infiltrative conditions: malignancies
Conditions associated with reduced erythropoietin production: renal failure
Where do we see increased RBC destruction?
Hereditary spherocytosis
sickle cell anemia
Glucose 6 phosphate dehydrogenase deficiency
Paroxysmal nocturnal hemoglobinuria (PNH)
Conditions leading to hypersplenism
Hemolytic anemia?
Anemias in which RBC destruction (hemolysis) is the cause of the anemia.
Hereditary causes: spherocytosis, PNH, G6PD deficiency, sickle cell anemia
Acquired hemolytic anemias may be autoimmune, drug-induced or traumatic (mechanical prosthetic heart valves)
Extravascular hemolysis?
RBCs are lysed outside the vasculature. Splenic macrophages or Kupffer cells in the liver destroy RBCs due to structural or morphological abnormalities
Hereditary spherocytosis, hypersplenism
Intravascular hemolysis?
RBCs are directly lysed within blood vessels.
PNH,
mechanical fragmentation by prosthetic valves or by fibrin clot products (as in microangiopathic hemolytic anemias which occur in DIC),
TTP (thrombotic thrombocytopenic purpura)
Haptoglobin
Serum protein that sops up free heme in circulation
Hemoglobinemia and hemoglobinuria in intravascular vs extravascular hemolysis
In intravascular, lysed RBCs spill their hemoglobin directly into the bloodstream (hemoglobinemia), which may then be filtered out into the urine (hemoglobinuria)
In extravascular, the phagocytosed hemoglobin is metabolized intracellularly to bilirubin
Haptoglobin will be more decreased in intravascular hemolysis than extravascular
MCV
Mean corpuscular volume
Used to determine RBC size
Calculated by dividing hematocrit by RBC count per liter
Normal reference range is 80-100fL
Normocytic, Microcytic, Macrocytic
based on relation to MCV
Normocytic, within normal MCV range
Microcytic: below
Macrocytic: Above range
Differentials for normocytic anemia
Anemia of chronic disease
Blood loss
Hemolytic anemias eg spherocytosis, PNH, G6PD deficiency, sickle cell anemia
Types of hemoglobin
Hemoglobin A (alpha2beta2) Hemoglobin A2 (alpha2delta2) Hemoglobin F (alpha2gamma2)
Differentials for microcytic anemia
Sideroblastic anemia Lead poisoning Thalassemia Iron deficiency Anemia of chronic disease
Diagnosis if gel electrophoresis reveals elevated A2 and F and complete absence of beta globin subunits
Beta thalassemia major (Cooley’s anemia)
Normal serum iron, ferritin and TIBC
Thalassemia major vs minor?
Zero vs partial expression of beta globin subunits
Minor is usually asymptomatic
Alpha thalasemia
Caused by reduced or absent synthesis of alpha globing chains
African and Southeast basin descent
HbH, Hb Barts
Structure of hemoglobin
Heme ring + 4 globing chains
Transition from HbF to HbA
By approximately six months of age, healthy infants will have transitioned to mostly HbA, a small amount of HbA2, and negligible HbF
Hemoglobin H
Alpha thalassemia intermedia
4 betas. No alpha globin chains produced
Hemolysis, severe anemia
Moderate to severe hemolytic anemia, modest degree of ineffective erythropoiesis, splenomegaly, variable bone changes
Hb Barts
Alpha thalassemia major
4 gammas. No alphas. Hydrops fetalis. Incompatible with life
Alpha globin chain production
controlled by two genes on each chromosome 16
A single gene deletion results in alpha thalassemia silent carrier status, which is asymptomatic with normal hematologic findings.
The two-gene deletion causes alpha thalassemia trait (minor) with microcytosis and usually no anemia.
The three-gene deletion results in significant production of hemoglobin H (HbH). Microcytic anemia, hemolysis, and splenomegaly.
The four-gene deletion results in significant production of hemoglobin Bart’s (Hb Bart’s),
Beta thalassemia
deficient or absent synthesis of beta globin chains
Beta thalassemia occurs from any of more than 200 point mutations and (rarely) deletions of the two genes.
Beta globin synthesis?
controlled by one gene on each chromosome 11
Beta thalassemia types
The one gene defect, beta thalassemia trait (minor), is asymptomatic and results in microcytosis and mild anemia.
If the synthesis from both genes is severely reduced or absent, the person has beta thalassemia major, also known as Cooley anemia.
Symptoms: Anemia, jaundice, splenomegaly at 6 months due to switch from fetal to adult hemoglobin. Asymptomatic at birth
beta thalassemia intermedia: Two defective genes, but synthesis if beta chains is less severely reduced. Less severe symptoms. Do not require lifelong blood transfusions
hemoglobin electrophoresis is usually normal in adults with alpha thalassemia trait.
T/F
True
Persons with beta thalassemia major are diagnosed during infancy.
Y/N
Yes!
Pallor, irritability, growth retardation, abdominal swelling, and jaundice appear during the second six months of life
complications that occur with beta thalassemia major or intermedia
overstimulation of the bone marrow, ineffective erythropoiesis, and iron overload from regular blood transfusions.
With multiple blood transfusions and continued absorption of intestinal iron, iron overload develops. Iron is deposited in visceral organs (mainly the heart, liver, and endocrine glands), and most patient deaths are caused by cardiac complications.
In Beta thalassemia major, which becomes the dominant hemoglobin
HbF
Complications of iron overload
Liver disease, pancreatic dysfunction (diabetes mellitus), cardiomyopathy
Chelation therapy is treatment for iron overload
